How Zika affects the extracellular matrix

In some cases, Zika virus (ZIKV) infection during pregnancy leads to a series of severe defects in the fetus collectively known as congenital Zika syndrome (CZS). These include microcephaly, defective neuronal migration, and impaired cortical development. Aguiar et al. combined genomic, transcriptomic, and proteomic analyses of blood and postmortem brains and demonstrated that ZIKV-infected neonates showed a reduction in collagen expression and an increase in adhesion factor expression, alterations in the extracellular matrix consistent with the brain defects seen in CZS. Together, these datasets form a useful resource for those investigating the molecular mechanisms underlying CZS in humans.

Zika virus (ZIKV) infection during pregnancy can cause a set of severe abnormalities in the fetus known as congenital Zika syndrome (CZS). Experiments with animal models and in vitro systems have substantially contributed to our understanding of the pathophysiology of ZIKV infection. Here, to investigate the molecular basis of CZS in humans, we used a systems biology approach to integrate transcriptomic, proteomic, and genomic data from the postmortem brains of neonates with CZS. We observed that collagens were greatly reduced in expression in CZS brains at both the RNA and protein levels and that neonates with CZS had several single-nucleotide polymorphisms in collagen-encoding genes that are associated with osteogenesis imperfecta and arthrogryposis. These findings were validated by immunohistochemistry and comparative analysis of collagen abundance in ZIKV-infected and uninfected samples. In addition, we showed a ZIKV-dependent increase in the expression of cell adhesion factors that are essential for neurite outgrowth and axon guidance, findings that are consistent with the neuronal migration defects observed in CZS. Together, these findings provide insights into the underlying molecular alterations in the ZIKV-infected brain and reveal host genes associated with CZS susceptibility.

Go here to read the rest:
Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome - Science

Spinal Cord Stem Cells Comments Off on Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome – Science | June 10th, 2020

Stem cell characterization is the study of tissue-specific differentiation. Thera are various type of stem cell such as embryonic stem cell, epithelial stem cell and others. Further, various techniques are used to characterized stem cells such as immunological techniques, used for depiction of different population of stem cells. These techniques are generally based on immunochemistry using staining technique or florescent microscopy. Besides, stem cells characterization and analysis tools are used against target chronic diseases. In 2014, the San Diego (UCSD) Health System and Sanford Stem Cell Clinical Center at the University of California announced the launch of a clinical trial, in order to assess the safety of neural stem cellbased therapy in patients with chronic spinal cord injury.

The factors driving the growth of stem cell characterization and analysis tools market due to increasing chronic disorders such as cancer, a diabetes and others. In addition, increasing awareness about among people about the therapeutic potency of stem cells characterization in the management of effective diseases is anticipated to increase the demand for stem cell characterization and analysis tools. Further, there are various technologies such as flow cytometry which is used to characterize the cell surface profiling of human-bone marrow and other related purposes are expected to increase the growth of stem cell characterization and analysis tools market. In addition, increasing investment by private and public organization for research activities are likely to supplement the market growth in near future.

Get Free Sample Copy With Impact Analysis Of COVID-19 Of Market Report @https://www.persistencemarketresearch.com/samples/31444

On the other hand, the unclear guidelines and the technical limitation for the development of the product are expected to hamper the growth of stem cell characterization and analysis tools market.

Rapid increase in corona virus all around the world is expected to hamper the growth of stem cell characterization and analysis tools market. The virus outburst has become one of the threats to the global economy and financial markets. The impact has made immense decrease in revenue generation in the field of all healthcare industry growth for the market in terms of compatibility and it has led in huge financial losses and human life which has hit very hard to the core of developing as well as emerging economies in healthcare sector. It further anticipated that such gloomy epidemiological pandemic environment is going to remain in next for at least some months, and this is going to also affect the life-science market which also include the market of stem cell characterization and analysis tools market.

Based on the Products and Service Type, stem cell characterization and analysis tools market are segmented into:

Based on the Technology, stem cell characterization and analysis tools market are segmented into:

Based on the Applications, stem cell characterization and analysis tools market are segmented into:

Based on the End User, stem cell characterization and analysis tools market are segmented into:

Based on the segmentation, human embryonic stem cell is expected to dominate the market due to their indefinite life span and higher totipotency as compared to other stem cells. Further, on the basis of technology segmentations, cell production is anticipated to increase the demand for stem cell characterization and analysis tools due to their emerging applications for stem cells in drug testing in the management of the effective diseases. Furthermore, on the basis of application segmentations, oncology is expected to show significant growth rate due to increase in the number of pipelines products for the treatment of cancers or tumors. Based on the end user, pharmaceutical and biotechnology companies are expected to dominate the market due to rising global awareness about the therapeutics research activities.

You Can Buy This PMR Healthcare Report From Here @https://www.persistencemarketresearch.com/checkout/31444

Geographically, the global stem cell characterization and analysis tools market is segmented into regions such as Latin America, Europe, North America, South Asia, East Asia Middle East & Africa and Oceania. North America is projected to emerge as prominent market in the global stem cell characterization and analysis tools market due to growing cases of target chronic diseases and increasing investments for research activities. Europe is the second leading region to dominate the market due to technological advancement and also surge in therapeutic activities, funded by government across the world. Asia-pacific is likely to witness maximum growth in near future due to increasing disposable income and with the development of infrastructure.

Some of the major key players competing in the global stem cell characterization and analysis tools market are Osiris Therapeutics, Inc., Caladrius Biosciences, Inc., U.S. Stem Cell, Inc., Astellas Pharma Inc., TEMCELL Technologies Inc., BioTime Inc., Cellular Engineering Technologies Inc., Cytori Therapeutics, Inc., and BrainStorm Cell Therapeutics Inc.

Rustil is a regular contributor to blog , Specializing in Industry Research and Forecast

See the original post:
Augmenting Demand for Stem Cell Characterization and Analysis Tools to Bolster Global Market Revenue Growth During the Crisis Period of COVID 19 - The...

Spinal Cord Stem Cells Comments Off on Augmenting Demand for Stem Cell Characterization and Analysis Tools to Bolster Global Market Revenue Growth During the Crisis Period of COVID 19 – The… | June 10th, 2020

The Covid-19 (coronavirus) pandemic is impacting society and the overall economy across the world. The impact of this pandemic is growing day by day as well as affecting the supply chain. The COVID-19 crisis is creating uncertainty in the stock market, massive slowing of supply chain, falling business confidence, and increasing panic among the customer segments. The overall effect of the pandemic is impacting the production process of several industries including Life Science, and many more. Trade barriers are further restraining the demand- supply outlook. As government of different regions have already announced total lockdown and temporarily shutdown of industries, the overall production process being adversely affected; thus, hinder the overall Silicone Foley Catheter Market globally. This report on Silicone Foley Catheter Market provides the analysis on impact on Covid-19 on various business segments and country markets. The report also showcase market trends and forecast to 2027, factoring the impact of Covid -19 Situation.

Download a Sample Report Explore further @ https://www.theinsightpartners.com/sample/TIPRE00011300/

Silicone foley catheter is a technique to purify cell populations based on the presence or absence of specific physical characteristics. Silicone foley catheter allows the separation of cells based on their intra- or extracellular properties, including DNA, RNA, and protein interactions, size, and surface protein expression. This is a unique attribute of many stem cell populations, including hematopoietic, embryonic, and cancer stem cells.

The silicone foley catheter market is expected to grow due to the increasing demand from emerging market. However, potential risks associated with the use of Foley catheters and presence of alternative treatments for urinary incontinence is hampering the market growth. Moreover, increasing development in development of medical devices industry, pharmaceutical, and biotechnology industries, increasing prevalence of urologic diseases is boosting the market growth in the upcoming year.

Top Dominating Key Players:

1. AngioDynamics2. B.Braun3. Bard Medical4. Boston Scientific5. Coloplast6. ConvaTec7. Cook Medical Inc.8. Hollister9. Medtronic plc10. Teleflex

The silicone foley catheter market is segmented on the basis of product type and application. Based on product type, the market is segmented as short-term foley catheters and long-term foley catheters. On the basis of application, the market is categorized as prostate gland surgery, urinary retention, urinary incontinence and spinal cord injury.

The study conducts SWOT analysis to evaluate strengths and weaknesses of the key players in the Silicone Foley Catheter Market. Further, the report conducts an intricate examination of drivers and restraints operating in the market. The report also evaluates the trends observed in the parent market, along with the macro-economic indicators, prevailing factors, and market appeal according to different segments. The report also predicts the influence of different industry aspects on the Silicone Foley Catheter Market segments and regions.

Scope of the study:

The research on the Silicone Foley Catheter Market focuses on mining out valuable data on investment pockets, growth opportunities, and major market vendors to help clients understand their competitors methodologies. The research also segments the Silicone Foley Catheter Market on the basis of end user, product type, application, and demography for the forecast period 20202027. Comprehensive analysis of critical aspects such as impacting factors and competitive landscape are showcased with the help of vital resources, such as charts, tables, and infographics.

Request for Buy Report @ https://www.theinsightpartners.com/buy/TIPRE00011300/

Reasons to Buy the Report:

About Us:

The Insight Partners is a one stop industry research provider of actionable intelligence. We help our clients in getting solutions to their research requirements through our syndicated and consulting research services. We are a specialist in Technology, Healthcare, Manufacturing, Automotive and Defense.

Contact Us:

The Insight partners,

Phone: +1-646-491-9876Email:[emailprotected]

Go here to read the rest:
Silicone Foley Catheter Market 2027: Which country will show the highest growth? - Cole of Duty

Spinal Cord Stem Cells Comments Off on Silicone Foley Catheter Market 2027: Which country will show the highest growth? – Cole of Duty | June 5th, 2020

GAITHERSBURG, Md., June 03, 2020 (GLOBE NEWSWIRE) -- OpGen, Inc. (Nasdaq: OPGN) announced today that its strategic collaboration with the New York State Department of Health (DOH) to develop a state-of-the-art solution to detect, track, and manage antimicrobial-resistant infections at healthcare institutions statewide is entering into its second year expansion phase. Having successfully achieved all of the milestones of the first year pilot phase for the development of an infectious disease digital health and precision medicine platform that connects healthcare institutions to DOH and uses genomic microbiology for statewide surveillance and control of antimicrobial resistance, OpGen will continue to work together with DOHs Wadsworth Center, participating healthcare systems, and collaborators such as Infectious Disease Connect, Inc. (IDC), which recently combined with ILM Health Solutions, to expand the reach of the platform, increase the volume of testing, and enhance data collection.

The DOH, OpGen, IDC and all stakeholders will continue to work collaboratively to demonstrate that a sustainable, flexible infectious diseases reporting, tracking and surveillance tool for antimicrobial resistance can be applied across New York State. The second-year expansion phase will build on the successes and experience of the first year pilot phase while focusing on accomplishing the goal of this visionary effort to improve patient outcomes and save healthcare dollars by integrating real-time epidemiologic surveillance with rapid delivery of antibiotic resistance results to care-givers via web-based and mobile platforms. OpGen is providing its Acuitas AMR Gene Panel for rapid detection of multidrug-resistant bacterial pathogens along with its Acuitas Lighthouse Software for high resolution pathogen tracking. The second year contract includes a quarterly retainer-based project fee as well as volume-dependent per test fees for a total contract value of up to $450,000 to OpGen.

We are excited and grateful that despite the continued threat of the COVID-19 pandemic which has hit New York State harder than any other place in the world, the Department of Health of New York State and the Wadsworth Center continue to work with us and have expanded their partnership for a second year, adding up to 3,500 AMR Gene Panel tests to be run, commented Oliver Schacht, CEO of OpGen. The quick spread of antimicrobial resistant superbugs across our healthcare systems is lurking below the current medical crisis. We anticipate that with our innovative diagnostic solutions we will be able to proactively identify such pathogens leading to early intervention and lifesaving treatment. A further project expansion of this nature may include the exploration of ways to achieve SARS-CoV-2 tracking.

Paul Edwards, Chief Strategy Officer at IDC commented, Our collaboration with OpGen allows us to not only identify bacteria and antimicrobial resistance down to the gene level but also to identify new or significant results versus phenotypic results alone. This molecular epidemiology capability in turn is critical in order to rapidly identify new clusters and outbreaks which otherwise would be missed and could potentially lead to outbreaks of hospital superbugs.

The precision medicine solutions provided by OpGen to accomplish the project goals are:

Wadsworth Center Director Dr. Jill Taylor said,"Under Governor Cuomo's leadership, New York State continues to lead the nation in addressing the threat of antimicrobial resistance. Working with our private-sector partners, the Wadsworth Center is able to further advance our mission to improve the public health of all New Yorkers.

About Antimicrobial-resistant InfectionsThe Centers for Disease Control and Prevention estimates that annually in the United States we face 2.8 million infections with 35,000 deaths and $49 billion in lost productivity all attributable to antibiotic resistant infections. Among the infectious diseases the parties are working to address are carbapenem-resistant Enterobacteriaceae (CRE) bacteria; they are untreatable and hard-to-treat infections on the rise among patients in medical facilities. CREs have become resistant to all or nearly all the antibiotics we have today. Almost half of hospital patients who get bloodstream infections from CRE bacteria die from the infection. The CDC has classified CREs as one of three urgent threats to the public health.

About Wadsworth Center LaboratoriesThe Wadsworth Center laboratories stand at the forefront of biomedical and environmental sciences and their interplay. The Center serves a vital role in the New York State Department of Healths efforts to protect and promote the health of New Yorks citizens. Building on more than a century of excellence as the states public health laboratory, the Center continues as a premier biomedical institute that merges clinical and environmental testing with fundamental, applied and translational research. Today, Wadsworth Center scientists use both classical and contemporary approaches to study environmental and biological questions related to human health and disease. They develop advanced methods to identify microbial or chemical threats; study drug resistance, emerging infections, and environmental exposures; manage the countrys most comprehensive diagnostic and environmental testing laboratory permit program; oversee extramural research programs on stem cells, breast cancer and spinal cord injury; and train the next generation of scientists through undergraduate, graduate, postdoctoral and visiting scientist programs.

About OpGen Inc.

OpGen, Inc. (Gaithersburg, MD, USA) is a precision medicine company harnessing the power of molecular diagnostics and bioinformatics to help combat infectious disease. Along with our subsidiaries, Curetis GmbH and Ares Genetics GmbH, we are developing and commercializing molecular microbiology solutions helping to guide clinicians with more rapid and actionable information about life threatening infections to improve patient outcomes, and decrease the spread of infections caused by multidrug-resistant microorganisms, or MDROs. OpGens product portfolio includes Unyvero, Acuitas AMR Gene Panel and Acuitas Lighthouse, and the ARES Technology Platform including ARESdb, using NGS technology and AI-powered bioinformatics solutions for antibiotic response prediction.

For more information, please visit http://www.opgen.com.

Forward-Looking Statements

This press release includes statements regarding OpGens second year project phase with the New York State DOH. These statements and other statements regarding OpGens future plans and goals constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and are intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. Such statements are subject to risks and uncertainties that are often difficult to predict, are beyond our control, and which may cause results to differ materially from expectations. Factors that could cause our results to differ materially from those described include, but are not limited to, our ability to successfully, timely and cost-effectively develop, seek and obtain regulatory clearance for and commercialize our product and services offerings, our ability to successfully complete the second phase of the project with the New York State DOH, the rate of adoption of our products and services by hospitals and other healthcare providers, the realization of expected benefits of our business combination transaction with Curetis GmbH, the success of our commercialization efforts, the impact of COVID-19 on the Companys operations, financial results, and commercialization efforts as well as on capital markets and general economic conditions, the effect on our business of existing and new regulatory requirements, and other economic and competitive factors. For a discussion of the most significant risks and uncertainties associated with OpGen's business, please review our filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which are based on our expectations as of the date of this press release and speak only as of the date of this press release. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

OpGen:Oliver SchachtPresident and CEO[emailprotected]

OpGen Press Contact:Matthew BretziusFischTank PR[emailprotected]

OpGen Investor Contact:Joe GreenEdison Group[emailprotected]

View original post here:
OpGen Expands Partnership with New York State Department of Health and IDC to Detect Antimicrobial-Resistant Infections - GuruFocus.com

Spinal Cord Stem Cells Comments Off on OpGen Expands Partnership with New York State Department of Health and IDC to Detect Antimicrobial-Resistant Infections – GuruFocus.com | June 3rd, 2020

In the UK 50,000 people have a spinal cord injury (SCI)[1]

Every year there are 2,500 new cases of SCI in the UK[1]

20-30% of people with SCI show clinically significant signs of depression[2]

People with spinal cord injury are two to five times more likely to die prematurely[2]

50kpeople in the UKhave spinal cord injury

A traumatic injury to the spine can cause a bruise, partial or complete tear in the spinal cord, leading to partial or total loss of feeling/movement in various body parts. The most common sites of injury are the cervical and thoracic areas.

Generally, spinal cord injuries (SCI) affect areas lower than the point of damage, so the higher the damage, the more movement and sensation will be lost. Spinal cord injury can even result in paraplegia and tetraplegia[3], although severity and recovery rate varies widely depending on the location and extent of the injury.

To aid recovery and lessen the risk of developing associated conditions, its essential that each patient receives appropriate rehabilitation and health maintenance support.

Stem cell therapy is rapidly evolving and offering treatment for spinal-cord injuries (SCI). Although there is no current treatment available to restore injury-induced loss of function, evidence is building that stem cell infusions into the spine may support spinal cord repair.

Positive results have been observed in phase I/II clinical trials at Puerta de Hierro Hospital in Madrid[4]. 12 patients were given doses of the new drug NC1 made from autologous mesenchymal stromal cells (MSCs) and autologous plasma. All 12 patients experienced improvements in sensitivity and 50% showed greater motor activity, decreased spasms and improved sexual function.

Since this clinical trial took place, the NC1 drug has been approved by the Spanish Agency of Medicines. However, there is still more research to be done for stem cell therapy to be widely administered for repairing spinal cord injury.

1. https://www.backuptrust.org.uk/spinal-cord-injury/what-is-spinal-cord-injury

2. https://www.who.int/news-room/fact-sheets/detail/spinal-cord-injury

3. https://www.spinal.co.uk/learn/understanding-sci/

4. https://www.sciencedirect.com/science/article/pii/S1465324916303772

Read the original:
Stem cell therapy and spinal cord injury (SCI) | Future ...

Spinal Cord Stem Cells Comments Off on Stem cell therapy and spinal cord injury (SCI) | Future … | May 31st, 2020

The spinal cord is a long, fragile, tube-like nervous structure that connects the brain with peripheral nerves. Damage to the spinal cord, by trauma or other means, consequently results in severe motor- and sensory deficits that usually lead to the inability to move and feel. Accidents are the most common cause of Spinal Cord Injury with catastrophic consequences for the life of the patient and their relatives. While conservative therapies aim to stabilize the patient, functional recovery in most cases is minimal.

Both preclinical and clinical studies have shown improved recovery of spinal cord injury patients when the therapy was combined with a suitable stem cell therapy. Our clinic provides access to the most advanced clinically available combination of stem cell therapies.

Spinal trauma can disrupt ascending and descending axonal pathways that lead to: inflammation, demyelination and loss of neural cells (neurons). Depending on the site of injury, functional disorders induced by cellular damage usually result in the inability to move, sensory loss and/or lack of autonomous nervous system control.

Fully regenerative therapies for spinal trauma do not exist yet. However, very promising results have been obtained with stem cell transplantation in patients with spinal trauma. The use ofMesenchymal Stem Cells (MSCs) in Spinal Cord Injury has been extensively reviewed. Experiments with MSCs have shown that their abilities to stimulate repair processes in spinal cord injury are due to the paracrine secretion of the stem cells. After 21 days of observations, even though the MSCs had not been incorporated into the regenerated host tissue, there was a significant improvement in functional recovery, from as early as one week after the treatment with MSCs.

Read the original:
Spinal Cord Stem Cell Treatments London | Regenerative ...

Spinal Cord Stem Cells Comments Off on Spinal Cord Stem Cell Treatments London | Regenerative … | May 31st, 2020

Central nervous system comprises brain and spinal cord, and is responsible for integration of sensory information. Brain is the largest and one of the most complex organs in the human body. It is made up of 100 billion nerves that communicate with 100 trillion synapses. It is responsible for the thought and movement produced by the body. Spinal cord is connected to a section of brain known as brain stem and runs through the spinal canal. The brain processes and interprets sensory information sent from the spinal cord. Brain and spinal cord serve as the primary processing centers for the entire nervous system, and control the working of the body. Neuroprosthetics improves or replaces the function of the central nervous system.

To remain ahead of your competitors, request for a sample [emailprotected] https://www.persistencemarketresearch.com/samples/4160

Neuroprosthetics, also known as neural prosthetics, are devices implanted in the body that stimulate the function of an organ or organ system that has failed due to disease or injury. It is a brain-computer interface device used to detect and translate neural activity into command sequences for prostheses. Its primary aim is to restore functionality in patients suffering from loss of motor control such as spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, and stroke. The major types of neuroprosthetics include sensory implants, motor prosthetics, and cognitive prosthetics. Motor prosthetics support the autonomous system and assist in the regulation or stimulation of affected motor functions.

Similarly, cognitive prosthetics restore the function of brain tissue loss in conditions such as paralysis, Parkinsons disease, traumatic brain injury, and speech deficit. Sensory implants pass information into the bodys sensory areas such as sight or hearing, and it is further classified as auditory (cochlear implant), visual, and spinal cord stimulator. Some key functions of neuroprosthetics include providing hearing, seeing, feeling abilities, pain relief, and restoring damaged brain cells. Cochlear implant is among the most popular neuroprosthetics. In addition, auditory brain stem implant is also a neuroprosthetic meant to improve hearing damage.

Request PMR insights on measuring the impact of COVID-19 coronavirus across industries.

North America dominates the global market for neuroprosthetics due to the rising incidence of neurological diseases and growth in geriatric population in the region. Asia is expected to display a high growth rate in the next five years in the global neuroprosthetics market, with China and India being the fastest growing markets in the Asia-Pacific region. Among the key driving forces for the neuroprosthetics market in developing countries are the large pool of patients, increasing awareness about the disease, improving healthcare infrastructure, and rising government funding in the region.

Increasing prevalence of neurological diseases such as traumatic brain injury, stroke and Parkinsons disease, rise in geriatric population, increase in healthcare expenditure, growing awareness about healthcare, rapid progression of technology, and increasing number of initiatives by various governments and government associations are some key factors driving growth of the global neuroprosthetics market. However, factors such as high cost of devices, reimbursement issues, and adverse effects pose a major restraint to the growth of the global neuroprosthetics market.

Innovative self-charging neural implants that eliminate the need for high risk and costly surgery to replace the discharge battery and controlling machinery with thoughts would help to develop opportunities for the growth of the global neuroprosthetics market.

The major companies operating in the global neuroprosthetics market are,

To receive extensive list of important regions, ask for TOC here @ https://www.persistencemarketresearch.com/toc/4160

Key geographies evaluated in this report are:

For in-depth competitive analysis, Check Pre-Book here @ https://www.persistencemarketresearch.com/checkout/4160

Key features of this report

Our unmatched research methodologies set us apart from our competitors. Heres why:

Read more from the original source:
Neuroprosthetics Market Scope and Opportunities Analysis Through 2021 - 3rd Watch News

Spinal Cord Stem Cells Comments Off on Neuroprosthetics Market Scope and Opportunities Analysis Through 2021 – 3rd Watch News | May 30th, 2020

INTRODUCTION

Embryonic development is characterized by the temporal and spatial regulation of cell proliferation, migration, differentiation, and tissue formation. Although these processes are genetically determined, several signaling mechanisms including Wnt have been recognized as essential in regulating cell lineage specification and organogenesis (13).

The Na/Kadenosine triphosphatase (ATPase) (NKA), discovered in crab nerve fibers by Skou (4), belongs to the P-type ATPase superfamily. It has an enzymatic function that couples adenosine 5-triphosphate (ATP) hydrolysis to the transmembrane movement of Na+ and K+ in a cell lineagedependent manner. For example, while the NKA is involved in the formation of action potentials in excitable cells, its polarized distribution is key to the functionality of the epithelium.

In addition to its canonical enzymatic function, we and others have shown that the NKA has an enzymatic activityindependent signaling function through its interactions with membrane cholesterol and proteins such as Src, epidermal growth factor (EGF) receptor, and caveolin-1 (58). We use the term signaling with liberty here, referring to the ability of NKA to work as a receptor, a scaffold, and a signal integrator by regulating the functions of its interacting proteins. This newly appreciated signaling function of the NKA has been implicated in several cellular processes (912). However, direct genetic evidence supporting a role for NKA signaling in animal physiology and disease progression is still lacking. This is due, in part, to the technical difficulties in studying its signaling separately from its ATPase-mediated pumping function because the latter is required for the survival of animal cells (13). Fundamentally, it is unknown whether the signaling function is an intrinsic property of the protein NKA, as its Na+- and K+-driven enzymatic activity has been recognized as. Therefore, we were prompted to address two important questions: (i) Were the signaling and Na+/K+ transport functions of the NKA coevolved? (ii) If so, does the signaling function of NKA represent a primordial yet common mechanism for the regulation of a fundamental process in animal biology?

Structurally, the NKA is composed of both and subunits. The subunit contains the binding sites for Na+/K+ as well as ouabain, which are distinct from that of other P-type ATPases (14). It also has an N-terminal caveolin binding motif (CBM) proximal to the first transmembrane helix (fig. S1A). To assess the functionality of this motif, we made F97A and F100A mutations that map to the rat 1 NKA sequence. This strategy has been used by others to study the function of CBM in proteins other than the NKA (15). We used a knockdown and rescue protocol to generate a stable cell line (LW-mCBM) that essentially expresses just the CBM mutant 1, which was confirmed using [3H]ouabain binding assays (fig. S1B). Western blot and confocal imaging analyses showed that the expression of mutant 1 NKA in LW-mCBM was comparable to that in the control cell line, named AAC-19 cells (fig. S1, B and C). The expression of CBM mutant 1 was sufficient to restore the expression of the 1 subunit of the NKA, allowing normal plasma membrane targeting of the CBM mutant NKA in LW-mCBM cells (fig. S1, C and D). The successful generation of a stable CBM mutant 1 cell line suggests that the CBM is not essential for the enzymatic activity of the NKA because the ion-transporting function is necessary for animal cell survival (13). In further support, we conducted kinetic studies of the CBM mutant NKA. As shown in Fig. 1A, the overall enzymatic activity per unit of 1 NKA expression was identical between the control AAC-19 and LW-mCBM cells. The Km values of Na+, K+, and ouabain were comparable between the CBM mutant NKA and control (Fig. 1, B to D) (16). Together, these data indicate that the N-terminal CBM is not directly involved in the regulation of the enzymatic properties of the NKA.

(A) Crude membrane preparations were made from AAC-19 and LW-mCBM cells and measured for ouabain-sensitive ATPase activity as described in Material and Methods. (B) Ouabain concentration curve. Crude membrane from LW-mCBM cells was prepared and measured for ATPase activity in the presence of different concentrations of ouabain. Data are shown as percentage of control, and each point represents three independent experiments. Curve fit analysis and IC50 (median inhibitory concentration) were calculated by GraphPad. (C and D) Measurements of Na+ and K+ Km. Assays were done as in (B). The combined data were collected from at least three repeats, and Km value (means SEM) was calculated using GraphPad.

On the basis of the above, we next turned our attention to determining the effects of the CBM mutation on signaling capabilities of the 1 NKA. Specifically, we first conducted immunoprecipitation experiments. As we reported previously in many types of cells (8), immunoprecipitation of caveolin-1 coprecipitated 1 in AAC-19 cells. In contrast, mutation of the CBM resulted in an over 80% decrease in coprecipitated 1 in LW-mCBM cells (Fig. 2A).

(A) Cell lysates from AAC-19 and LW-mCBM were immunoprecipitated (IP) with polyclonal anticaveolin-1 antibody. Immunoprecipitated complex was analyzed by Western blot for 1 and caveolin-1 (n = 4). **P < 0.01 compared to AAC-19. (B) Cell lysates from AAC-19 and LW-mCBM cells were subjected to sucrose gradient fractionation as described in Materials and Methods. A representative Western blot of three independent experiments was shown. **P < 0.01 in comparison to AAC-19. (C) AAC-19 and LW-mCBM cells were treated with different concentrations of ouabain for 10 min and analyzed by Western blot. A representative Western blot was shown (n = 4). *P < 0.05 versus 0 mM ouabain. (D) Cell growth curves of AAC-19 and LW-mCBM. *P < 0.05 versus AAC-19 cells. (E) BrdU assay of AAC-19 and LW-mCBM. The values are means SEM from at least three independent experiments. Photo credit: Xiaoliang Wang, Marshall Institute for Interdisciplinary Research at Marshall University.

To substantiate these observations, we next conducted a detergent-free and carbonate-based density gradient fractionation procedure and found that 1 NKA and its main signaling partners (Src and caveolin-1) were co-enriched in the low-density caveolar fractions, as previously reported in epithelial cells (8, 17). In sharp contrast, the expression of the CBM mutant 1 caused the redistribution of these proteins from low-density to high-density fractions (Fig. 2B). Quantitatively, when the ratios of fraction 4/5 of each protein versus total were calculated, we found that the low-density fraction 4/5 prepared from the control AAC-19 cells contained ~60, ~70, and 80% of caveolin-1, Src, and 1 NKA, respectively. However, in LW-mCBM cells, only ~20% of caveolin-1, Src, and 1 NKA were detected in fraction 4/5 (Fig. 2B).

To address the functional consequences of the dissociation of the 1 NKA from its signaling partners in LW-mCBM cells, we exposed these cells to ouabain, a specific agonist of the receptor NKA/Src complex. As shown in Fig. 2C, while ouabain stimulated phosphorylation of extracellular signalregulated kinase (ERK), a downstream effector of the NKA/Src signaling pathway in AAC-19 cells (5, 8), it failed to do so in LW-mCBM cells.

We have previously shown that 1 NKA signaling is key to the dynamic regulation of cell growth (16, 18). As shown in Fig. 2D, LW-mCBM cells grew much slower than AAC-19 cells. 5-Bromo-2-deoxyuridine (BrdU) incorporation assays further verified that the expression of CBM mutant 1 resulted in an inhibition of cellular proliferation (Fig. 2E). In short, the above in vitro experiments indicate that the gain of CBM enables the NKA to perform the enzymatic activityindependent signaling functions.

With the preceding in vitro data suggesting that the CBM is critically important to the signaling function of the NKA, we next set forth to test the physiological significance of this finding. Thus, we generated a knock-in mouse line expressing the aforementioned CBM mutant 1. The CBM mutant (mCBM) mouse was generated using the Cre/LoxP gene targeting strategy (19), as depicted in fig. S2A. The chimeric offspring were crossed to C57BL6 females to yield mCBM heterozygous mice, and the desired F97A and F100A substitutions were verified (fig. S2B). mCBM heterozygous mice were born fertile and survived to adulthood. Our attempts to generate mCBM homozygous mice yielded no viable homozygous pups (Fig. 3A) in nearly 400 young mice genotyped by polymerase chain reaction (PCR). These results document for the first time that the CBM in the 1 subunit of the NKA represents a fundamental signaling mechanism essential for mouse embryonic development and survival.

(A) Early embryonic lethality of mCBM homozygous embryos. (B) Morphological comparison and body size of wild-type (WT) (top), heterozygous (middle), and homozygous (bottom) mCBM embryos at E9.5. Black bars, 0.3 mm. The arrows show the abnormal head morphology. Body size was measured from at least 12 embryos in different genotypes by ImageJ. Data are presented as means SEM. ***P < 0.01 versus the average of WT. (C) Sagittal sections of WT and homozygous (Homo) and heterozygous (Het) embryos at E9.5 with hematoxylin and eosin (H&E) staining. Homozygous embryos that had defective brain development indicated by open arrows. (D) Brain cross section of WT, homozygous, and heterozygous embryos at E9.5 with H&E staining. Homozygous embryos that had unclosed neural tube in forebrain, midbrain, and hindbrain were indicated by arrows; WT and heterozygous E9.5 embryos with closed neural tube were indicated by arrowhead. (E) Morphological comparison of WT and Na/K-ATPase 1 (+/) embryos at E9.5. White bars, 0.3 mm (n = 5 to 7). Photo credit: Xiaoliang Wang, Marshall Institute for Interdisciplinary Research at Marshall University.

There is evidence that endogenous ouabain is important in animal physiology because of its role in stimulating the signaling function of the NKA (10, 19, 20). Because the loss of the CBM abolishes ouabain-induced signal transduction in vitro, we tested whether administration of pNaKtide, a specific inhibitor of the receptor NKA/Src complex (21), would cause the same embryonic lethality as we observed in mCBM mice. As depicted in fig. S3, we observed no change in fetal survival after administration of pNaKtide to female mice before mating and continued until the end of pregnancy. It is important to mention that pNaKtide has been proven to be specific and effective in blocking the NKA/Src receptor signaling in vivo (2226), and our control experiments showed that pNaKtide could cross the placental barrier. Moreover, this lack of pNaKtide effect on mouse embryogenesis appears to be consistent with a previous report demonstrating that neutralization of endogenous ouabain by injection of an anti-ouabain antibody did affect the kidney development of neonatal mice but did not affect their overall survival (20). On the basis of these, we concluded that the NKA/Src receptor function in the CBM mutant embryo was not the direct cause of lethality and set out to identify a hitherto unrecognized NKA CBM-dependent yet NKA-Srcindependent underlying mechanism.

Embryo implantation within mice occurs around embryonic day 4.5 (E4.5) (27), followed by gastrulation around E5.5 to E7.5 (28), when the simple embryo develops into an organized and patterned structure with three germ layers (29). Subsequently, organogenesis takes place at E8.0 and onward; the patterned embryo starts to develop its organ systems including the brain, heart, limbs, and spinal cord.

To further analyze and explore the molecular mechanisms of the CBM mutation in the embryonic development of mice, we harvested the fertilized eggs at E1.5, and cultured them in vitro. It has previously been demonstrated that 1 knockout results in the failure of blastocyst formation (13). In contrast, we found that eggs from mCBM heterozygous parents developed into morphologically normal blastocysts. These findings indicate that loss of the CBM does not affect the molecular mechanisms necessary for blastocyst formation. Thus, a loss of functional 1 CBM and complete knockout of 1 NKA both result in embryonic lethality but differ by their specific mechanisms. Knockout of 1 NKA inevitably causes the loss of NKA enzymatic function, which is incompatible with life (13), and results in the failure of blastocyst formation in mice. In contrast, our in vitro data indicate that a loss of the CBM does not cause any notable alteration in NKA enzymatic activity, which is supported by the observation that mCBM mice are still capable of producing morphologically normal blastocysts. Consequently, CBM role in development appears to be critical at a developmental stage beyond blastocyst stage, and we further set out to identify this stage.

To this end, we collected and genotyped embryos or yolk sacs from mCBM heterozygous mice at different days of gestation. We first dissected 31 embryos at E12.5 from three different mice (Fig. 3A). Reabsorption and empty deciduae were observed in six implantation sites with only the mothers genotype detectable. At E9.5, we were able to dissect a total of 303 embryos. Sixty-four of them were mCBM homozygous (21%), 71 were wild-type (23%), and 168 were mCBM heterozygous (55%) (Fig. 3A).

To further analyze the embryonic developmental defects, we examined mCBM embryos at E7.5, E8.5, and E9.5. The embryos looked similar between wild-type and mCBM homozygous mice at E7.5 and E8.5 under dissection microscopy. However, we found several severe morphological defects in homozygous embryos at E9.5 (Fig. 3, C and D). First, the overall size of embryos was considerably reduced in mCBM homozygous embryos (about 35% the size of the wild-type embryos). In addition, the observed effect of the CBM mutant on embryonic size was gene dose dependent, as the mCBM heterozygous embryos were significantly smaller than those of wild-type embryos but much bigger than the homozygous embryos. Second, most homozygous embryos did not turn, a process normally initiated at E8.5, suggesting that the loss of a functional CBM was responsible for a developmental arrest at an early stage of organogenesis. Last, the most severe morphological defects were observed in the heads of the mCBM homozygous embryos. In addition to the reduced size (about 25% of the size of wild-type embryos), we observed that mCBM homozygous embryos failed to close their cephalic neural folds (anterior neuropore) as indicated by the arrow in Fig. 3B. This phenotype more closely resembled wild-type embryos at E8.0 to E8.5, suggesting again that the loss of CBM arrested organogenesis in its early stages. On the other hand, all heterozygous embryos, although smaller than wild-type embryos, showed normal head morphology (Fig. 3B).

To follow up on the above observations, we collected and made histological sections of wild-type, heterozygous, and homozygous embryos at E9.5 (Fig. 3, C and D). Normally, formation and closure of the anterior neuropore occurs at E9.5 (Fig. 3D). In sharp contrast, mCBM homozygous embryos developed defects in neural closure. Specifically, failure of neural tube closure at the level of forebrain, midbrain, and hindbrain was prominent in homozygous embryos (Fig. 3D).

To further explore the molecular mechanism by which the loss of the CBM led to defects in organogenesis, we next conducted RNA sequencing analyses (RNAseq) in wild-type and mCBM homozygous embryos. More than 17,000 genes were read out in either mCBM homozygous or wild-type samples. Data analyses indicated that 214 and 208 genes from mCBM homozygous embryos were significantly down- and up-regulated, respectively (fig. S4). Among them, the expression of a cluster of transcriptional factors important for neurogenesis was significantly reduced. As depicted in Fig. 4A, the expression of neurogenin 1 and 2 (Ngn1/2), two basic helix-loop-helix (bHLH) transcriptional factors (30), was significantly down-regulated in homozygous embryos. Ngn1/2 are considered to be determination factors for neurogenesis, while members of the NeuroD family of bHLH work downstream to promote neuronal differentiation (31). We found that the expression of NeuroD1/4 was further reduced in mCBM homozygous embryos. As expected from these findings, the marker of neural stem cells nestin (Nes) and other genes related to neurogenesis including huntington-associated protein 1 (Hap1), nuclear receptor subfamily 2 group E members 1 (Nr2e1), and adhesion G protein (heterotrimeric guanine nucleotidebinding protein)coupled receptor (Adgrb1) were all down-regulated in mCBM homozygous embryos (Fig. 4A). To verify these data, we performed reverse transcription quantitative PCR (RT-qPCR) analyses of both wild-type and mCBM homozygous embryos collected at E9.5. As depicted in Fig. 4 (B to D), the aforementioned transcriptional factors were all down-regulated in a cascade fashion. While a modest reduction was found with Ngn1/2, the expression of NeuroD1/4 was almost completely inhibited. To test whether the effects of the CBM mutation on the expression levels of these transcriptional factors were gene dose dependent, we also examined mRNA levels of Ngn1/2 and NeuroD1/4 in mCBM heterozygous embryos. As depicted in Fig. 4 (B and C), the expression of these genes followed the pattern found in homozygous embryos. The expression level in heterozygous embryos was significantly reduced compared to wild-type embryos but was much higher than that of mCBM homozygous embryos. These gene dosingdependent cascade effects suggest that the 1 NKA is an important upstream regulator but not a determinant of neurogenesis like Ngn1/2 (32) or a key receptor mechanism like Wnt is.

(A) RNAseq results of several neurogenesis and neural stem cell markers. Log2 ratio = 1 means twofold of change. *P < 0.05 compared to WT. (B and C) RT-qPCR analysis of selected gene expression in WT, heterozygous, and homozygous mCBM embryos at E9.5. (D) RT-qPCR analysis of neural stem cell marker gene expression in WT and homozygous mCBM E9.5 embryos. (E) RT-qPCR analysis of neurogenesis marker genes in WT and NKA 1+/ mouse E9.5 embryos. Quantitative data are presented as means SEM from at least six independent experiments. *P < 0.05, **P < 0.01 versus WT control.

As a control, we also assessed the expression of different isoforms of NKA and caveolin-1. As depicted in fig. S5, no changes were detected in the expression of the 1 isoform of the NKA. This is expected, as the mutations were only expressed on exon 4. Previous reports have demonstrated that, in addition to the 1 isoform, neurons also express the 3 isoform, while muscle and glial cells express the 2 isoform of the NKA (9). No difference was observed in the expression of 3, while the expression of 2 was too low to be measured. We were also unable to detect any change in the expression of caveolin-1.

The total amount of protein recognized by the anti-NKA 1 antibody is unchanged in mCBM heterozygous mouse tissues compared to that of the wild type, albeit with changes in distribution in caveolar versus noncaveolar fractions. This indicates that the CBM mutant protein is fully expressed, as observed in cells (fig. S1), and further demonstrates that a reduction of enzymatic activity is not responsible for the observed phenotype in mCBM homozygous embryos. However, because the expression of wild-type 1 in mCBM heterozygous animals is most likely reduced, the phenotypic changes we observed in these mice could be due to the reduction of wild-type 1 expression rather than the expression of CBM mutant 1. To address this important issue, we collected embryos from 1 NKA heterozygous (1+/) mice and their littermate controls (33). In contrast to mCBM heterozygotes, reduction of 1 expression alone did not change the size of embryos (Fig. 3D), head morphology, or the expression of neuronal transcriptional factors (Fig. 4E). Because NKA 1 haploinsufficiency did not phenocopy mCBM heterozygosity, it was concluded that the mCBM allele was responsible for the observed changes.

The CBM in NKA has a consensus sequence of FCxxxFGGF (fig. S6). To assess the generality of CBM-mediated regulation, we first turned to the conserveness of the CBM in animal NKA. A database search reveals that, like Wnt, the mature form of NKA (i.e., containing CBM, Na+/K+ binding sites, and subunit) is absent in unicellular organisms but present in all multicellular organisms within animal kingdom (fig. S6). Further analysis of published data confirms the coevolutionary nature of the CBM and the binding sites for Na+ and K+ in the NKA. The first indication is from the analysis of single-cell organisms. No mature form of NKA is found in these organisms (fig. S6A). However, Salpingoeca rosetta, a marine eukaryote belonging to the Choanoflagellates class, undergoes a very primitive level of cell differentiation and specialization in their life cycle and expresses a putative NKA with several conserved motifs involved in the binding of Na+/K+. On the other hand, it contains no CBM (fig. S6) and there is also no evidence that it expresses a subunit.

Second, as depicted in figs. S6 and S7, Caenorhabditis elegans, an example of a metazoan organism, expresses a mature form of NKA (eat-6) that contains binding sites for Na+ and K+ as well as the N-terminal CBM. It also expresses a couple of putative NKA such as catp-2 (34). However, they contain neither the CBM nor Na+ and K+ binding sites.

Third, although the X amino acids in the NKA CBM in invertebrates vary, only conserved substitutions occurred in this motif. This is in sharp contrast to many other membrane receptors/transducers such as Patched and G that also contain a consensus CBM (figs. S6 and S7). Within vertebrates, the CBM sequence FCRQLFGGF in NKA remains completely conserved across all species. Moreover, this sequence remains conserved in all isoforms of the subunit except for the 4 isoform, which is exclusively expressed in sperm. The 4 isoform in some species still adapts the CBM sequence found in invertebrates (fig. S6). Moreover, of a total of nine subunits found in zebrafish (35), five appear to be 1 homologs that, like the 4 isoform, contain both vertebrate and invertebrate CBM sequences.

Last, turning to the evolutionary aspect of the receptor NKA/Src complex, we found that the Src-binding NaKtide and Y260 sequences, in sharp contrast to the CBM, are only conserved in mammalian ATP1A1 (fig. S7). Therefore, the NKA/Src receptor may have evolved after the acquisition of the CBM, and hence is not a part of the fundamental regulation of animal organogenesis (fig. S3).

In short, the N-terminal CBM, like the binding sites for Na+ and K+, is conserved in all subunits of NKA in animals, even after taking into consideration gene duplications and the generation of different isoforms or homologs. Thus, we postulate that this CBM must be evolutionally conserved to enable the NKA, in parallel with its enzymatic function, to serve an important role in the origination of multicellular organisms within the animal kingdom.

Organogenesis represents a unique feature of multicellular organisms. In considering the preceding findings, we reasoned that the loss of NKA CBM would also affect embryonic development in invertebrates such as C. elegans. To test our hypothesis, we used CRISPR-Cas9 to knock in the equivalent CBM double mutations of F75A and F78A in C. elegans NKA gene eat-6 (named as syb575) (fig. S8). Similar to the impact of the expression of CBM mutant 1 NKA in mice, no homozygous worms were produced, whereas the heterozygous worms hatched normally. Moreover, by using the gene balancer nT1, we confirmed that the F75A and F78A double mutations induced embryonic lethality in syb575 homozygotes secondary to L1 arrest (Fig. 5A). Furthermore, the observed larval arrest due to the loss of the eat-6 CBM was rescued by a transgene expressing a wild-type eat-6 complementary DNA (cDNA) through an extrachromosomal array (Fig. 5B). The lethality phenotype in syb575 mutants was different from those of the eat-6 mutants defective in enzymatic (transport) activity, because while the eat-6 mutants had growth defects, they were able to grow past the L1 stage (36). An exception to this was a cold-sensitive eat-6 (ad792) mutant with severely reduced transport activity, which exhibited L1 arrest at lower temperatures similarly to the syb575 mutant worms (36). Overall, those data suggest that both CBM-mediated signaling and ion transport activity by the NKA are essential to full-scale organogenesis in C. elegans.

(A) Heterozygous CBM mutant (mCBM) worms syb575/nT1 have GFP signals in pharynx (pointed with the arrowhead), while mCBM homozygous worms are GFP negative and arrested at larval stage (pointed with an arrow). (B) Rescue with a WT eat-6 gene showing a mCBM homozygous worm with a transgenic marker sur-5::GFP. Arrow points the somatic GFP signals. (C) Mutation of CBM1 NKA (F97A; F100A) results in reduced colony formation in human iPSC (mCBM iPSC). (D) RT-qPCR analysis of stem cell markers and primary germ layer markers in WT and mCBM iPSC. *P < 0.05 compared to WT. n = 7. Photo credit: Liquan Cai, Marshall Institute for Interdisciplinary Research at Marshall University.

In short, our data indicate that loss of the NKA CBM results in defective organogenesis in both mice and C. elegans. This, together with our finding that the NKA CBM is conserved in all NKA regardless of isoform or homolog, indicates that the NKA was originally evolved as a dual functional protein in multicellular organisms, and that it represents a primordial and common mechanism for regulating stem cell differentiation and early stage of organogenesis in animals.

Turning now to even more general features of the CBM in organogenesis, we searched for the plant plasma membrane H-ATPase that functions equivalently to the animal NKA. Like the NKA, the plant plasma membrane H-ATPase also contains a sequence motif at the first transmembrane segment that is in accordance with the consensus CBM. This motif is completely conserved from blue algae to land plants but does not exist within yeast and bacteria (fig. S6).

To assess the human relevance of our findings, we used CRISPR-Cas9 gene editing to generate the same mutations in human induced pluripotent stem cells (iPSCs) (fig. S9). As depicted in Fig. 5C, the expression of mutant CBM 1 reduced the colony formation ability of human iPSCs. Concomitantly, this was accompanied by a significant reduction in the expression of stemness markers (both Nanog and Oct4), and transcriptional factors controlling germ layer differentiation (gene MIXL and T for mesoderm, OTX2 and SOX1 for ectoderm, and GATA4 and SOX17 for endoderm) (Fig. 5D). These findings confirm an essential role of the NKA CBM in the regulation of stem cell differentiation and suggest the potential utility of targeting the NKA for improving tissue regeneration.

The canonical Wnt pathway is made of multiple components localized in the plasma membrane and cytosol (2, 3). Functionally, this pathway is critically important in animal organogenesis (2, 37). For example, it plays an essential role in the establishment of neurogenic niches and regulates the differentiation of neural stem cells into neuroblasts during organogenesis by regulating the expression of transcriptional factors Ngn and NeuroD (37, 38). Thus, we were prompted by the observed neural defects in mice to test whether the expression of the CBM mutant 1 NKA affects Wnt/-catenin signaling.

In the first set of studies, we examined the cellular distribution of -catenin in LW-mCBM cells. As depicted in Fig. 6A, confocal imaging analysis showed that -catenin was distributed away from the plasma membrane in a vesicle-like form in LW-mCBM cells. To verify this finding, we fractionated the cell lysates as performed in Fig. 3B and observed that -catenin, like Src and caveolin-1, moved from the low-density fractions to high-density fractions when compared to control cells (Fig. 6B). Control experiments showed no changes in the expression of E-cadherin, glycogen synthase kinase3 (GSK-3), LRP5/6 (Low-density lipoprotein receptor-related protein 5 and 6), and -catenin in LW-mCBM cells (Fig. 6C).

(A) -Catenin staining of AAC-19 and LW-mCBM at basal level (n = 5). Blue arrow indicated -catenin signal in the cytoplasm of cells. (B) Sucrose gradient fractionation of -catenin in AAC-19 and LW-mCBM cells (n = 3). **P < 0.01. (C) Western blot analysis of Wnt/-catenin signaling proteins in AAC-19, LX-2, and LW-mCBM cells from at least six independent experiments. Two samples from each cell lines are presented. (D) Wnt3a induced TOPFlash luciferase report assay in AAC-19 and LW-mCBM (n = 8). ***P < 0.01. (E) Wnt3a induced expression of Wnt/-catenin targeting genes (n = 8). **P < 0.01. (F) Wnt3a induced TOPFlash luciferase report assay in AAC-19, LX-2, and LW-mCBM cells (n = 4). ***P < 0.01.

To test whether these changes in -catenin distribution alter the function of canonical Wnt signaling, we conducted a TOPFlash luciferase activity assay (39). Cells were transiently transfected with the reporter plasmid, exposed to Wnt3a conditional medium, and then subjected to TOPFlash luciferase assays. As shown in Fig. 6D, while Wnt3a induced a greater than 35-fold increase in luciferase activity in AAC-19 cells, it only produced a fourfold increase in LW-mCBM cells, which equates to an approximate 90% reduction in the dynamics of Wnt activation. To further test the impact of the CBM mutation on Wnt signaling, we examined the effects of Wnt3a on the expression of Wnt target genes. Cells were exposed to Wnt3a for 6 hours and subjected to RT-qPCR analysis. As depicted in Fig. 6E, while Wnt3a increased the expression of c-Myc, Lef, and NKD1 expression in AAC-19 cells, it failed to do so in LW-mCBM cells.

On the basis of the above observations, we reasoned that the NKA CBM might play an essential role in the dynamic regulation of Wnt signaling. We therefore analyzed Wnt signaling in our LX-2 cell line. This cell line was made by the same strategy used for the generation of LW-mCBM cells, and it expresses essentially just the 2 isoform (40). We have observed that 2 NKA, like CBM mutant 1, maintains cellular pumping capacity but is unable to signal via Src like a wild-type 1 NKA (40). However, unlike CBM mutant 1, 2 does contain the same CBM at the N terminus (fig. S6). As depicted in Fig. 6F, expression of the 2 isoform produced a rescue of Wnt signaling dynamics when compared to that in LW-mCBM cells, which reinforces the idea that the NKA CBM is key to the dynamics of Wnt signaling. Like in LW-mCBM cells, no change in -catenin expression was noted in LX-2 cells. However, compared to LW-mCBM cells, caveolin-1 expression was decreased in LX-2 cells, while ERK activity was increased (Fig. 6C). Together, these findings suggest that the conserved NKA CBM is essential for regulating Wnt signaling, which is independent of the pumping or CTS (ardiotonic steroid)activated Src-dependent signaling transduction.

To see whether there is evidence of Wnt signaling defects in mCBM homozygous embryos, we examined the RNAseq data using a tool kit of pathway analysis. As depicted in fig. S10, Wnt signaling appears to be defective at the transcriptional level. First, the expression of one of the Wnt receptors [Frizzled homolog 5 (Fzd5)] and one of the Wnt ligands (Wnt7b) was down-regulated (fig. S10A). Second, the Wnt/-catenin signaling inhibitor, secreted frizzled-related protein 5 (Sfrp5), was up-regulated in mCBM homozygous embryos. Third, the -catenin destruction complex component adenomatosis polyposis coli (APC) was down-regulated in mCBM homozygous embryos. All these defects in Wnt signaling were confirmed by RT-qPCR analysis of both wild-type and mCBM homozygous embryos at E9.5 (fig. S10B). In addition, APC down-regulation was also observed at the protein level in mCBM iPSCs (fig. S10C). Last, the defect in Wnt signaling was further substantiated by the altered expression of Wnt downstream target genes. As shown in fig. S10B, the expression of Lef and NKD1 was significantly reduced in mCBM homozygous embryos. The expression of c-Myc was too low to be detected.

Together, these data provide strong support to the notion that the CBM is a key to the regulation of Wnt by the NKA. We hypothesize that this critical function of the NKA CBM may explain why the CBM is conserved in all four subunit isoforms of the NKA. It is important to mention that the specific molecular defects in Wnt signaling that we have identified were tested in epithelial cells, a model we have previously used to characterize 1-specific signaling functions (16, 41). In view of the cell/tissue specificity of both NKA expression and subunit assemble (42) and Wnt signaling (13, 37), it is likely that this mechanism does not fully explain the Wnt signalingrelated defects in embryogenesis.

The enzymatic function of NKA coordinates the transmembrane movement of Na+/K+, which is essential for the survival of individual animal cells. At the tissue/organ level, the ATP-powered transport of Na+/K+ by the NKA is required for neuronal firing, muscle contraction, and the formation and functionality of epithelia and endothelia. The NKA was found to be essential for forming septate junction in Drosophila melanogaster (43, 44) via a regulatory mechanism independent of its ion-pumping activity. Here, we reveal an additional fundamentally important role of NKA in the regulation of signal transduction through a separate functional domain (CBM) unrelated to its enzymatic activity.

Our findings raise the question of why NKA acquired the CBM in addition to its binding sites for Na+ and K+. One possible explanation for this is that the additional functionality in NKA (fulfilled by the CBM) evolved for the purpose of regulating stem cell differentiation and organogenesis in multicellular organisms. Two observations support this hypothesis. First, both Wnt and NKA are present in the first multicellular organisms within the animal kingdom and are evolutionally conserved ever since. Thus, it is likely that the NKA and Wnt work in concert to enable stem cell differentiation and organogenesis in animals. Second, while Wnt is key to the cellular programs of stemness and cell lineage specification (2), it does not directly participate in cell lineagespecific activities of newly differentiated cells. Instead, this particular function might be fulfilled by the NKA. Conceivably, the NKA could have been evolved, as exemplified by the mitochondrial cytochrome c in ATP generation, to bring together two seemingly unrelated processes (i.e., Wnt signaling regulation via the CBM and ion transport through Na+ and K+ binding) into one signaling circuitry, which is critical to the dynamic regulation of transcriptional factors that are required for organogenesis in a temporally and spatially organized manner. Needless to say, this hypothesis remains to be tested. In addition, other important signaling pathways such as Notch and Sonic Hedgehog may also be regulated by NKA.

It is also of interest to note the evolutionary conserveness of the CBM in the plant plasma membrane H-ATPase. Like its counterpart within the animal kingdom, the plasma membrane H-ATPase is essential for plant organogenesis (45). Unlike the NKA, the plasma membrane H-ATPase exists in single-celled organisms such as yeast, and their ion-pumping function is regulated by similar mechanisms (46). However, yeast, with no use for cellular machinery needed for organogenesis, does not contain the H-ATPase with conserved CBM. Moreover, we also observed that no CBM exists in the plasma membrane Ca-ATPase (fig. S6), both of which belong to the same type II P-type ATPase family as the NKA. While the Ca-ATPase is a more ancient protein than the NKA, as its expression can be found in unicellular organisms, the H/K-ATPase appeared later than the NKA, at some point during the development of vertebrates. Thus, we suggest that the NKA may have evolved from a P-ATPase of unicellular organisms via the gain of both the CBM and Na+/K+ binding sites. In contrast, the H/K-ATPase may have evolved from the NKA, losing not only the Na+ binding site but also the CBM.

We have shown a direct interaction between the NKA and caveolin-1 (8, 17), which has been independently confirmed (47). The loss of the CBM significantly reduced the interaction between NKA and caveolin-1 as revealed by multiple assays. In addition to caveolin-1, we and others have reported several signal transductionrelated interactions (48). Of these, the potential interaction between 1 NKA and Src has attracted the most attention, especially in the past 10 years (7). While most studies indicated an important role of Src in CTS-activated signal transduction via 1 NKA, several publications have questioned whether 1 NKA interacts with Src directly to regulate Src functionality (49, 50). While this important difference remains to be experimentally addressed, we would like to point out the following facts. First, while we recognize the merit of using purified protein preparation to study protein interaction, it is important to recognize the limitation of using purified Src from bacterial expression system because they are heterogeneously phosphorylated. Second, we have reported multiple lines of evidence that support a direct interaction between 1 NKA and Src, including the identification of isoform-specific Src interaction, the mapping of potential Src-interacting sites in the 1 isoform, and the development of pNaKtide as Src inhibitor and receptor antagonist. These findings have substantially increased our understanding of 1 NKA/Src interaction in cell biology and animal physiology. It is important to mention that several groups not associated with us have successfully used pNaKtide to block ouabain and NKA signaling in vitro and in vivo (2326, 51). While our group and others continue to characterize the molecular basis and biological function of the NKA/Src receptor complex, we propound that the question of NKA/caveolin-1 interaction is a more pressing one in the context of this study. The role of CBM in caveolin-protein interaction and caveolae-related signaling is still debated (41, 52, 53).

Last, we conclude from these interesting findings that the NKA is not just an ion pump or a CBM-directed regulator but a critical multifunctional protein. This whole functionality underlies a hitherto unrecognized common mechanism essential for stem cell differentiation and organogenesis in multicellular organisms within the animal kingdom. Moreover, many recent studies also support the concept that the 1 NKA has acquired more functional motifs (e.g., Src-binding sites for the formation of NKA/Src receptor complex) during evolution. In addition, we have demonstrated that either knockdown of 1 NKA or the expression of an N-terminal fragment containing the CBM of the 1 subunit was sufficient to attenuate purinergic calcium signaling in renal epithelial cells (54). The 1 NKA is also found to be essential for CD36 and CD40 signaling in macrophages and renal epithelial cells (55, 56). Aside from the profound biological and fundamental implications, the previously unidentified NKA-mediated regulation of Wnt signaling through its N-terminal CBM may have substantial implications in our understanding of disease progression. The rapidly increasing appreciation of Wnt signaling in the pathogenesis of cancer and cardiovascular diseases (2, 3, 38) underlies the potential utility of NKA as a multidrug target (12, 22, 57, 58).

Acknowledgments: Funding: This work was supported by grants from: National Institutes of Health (NIH) Research Enhancement Award (R15) (R15 HL 145666); American Heart Association (AHA) Scientist Development Grant (#17SDG33661117); Brickstreet Foundation and the Huntington Foundation, which provide discretionary funds to the Joan C. Edwards School of Medicine. (These funds are both in the form of endowments that are held by Marshall University). Author contributions: Conceptualization: Z.X., X.W., J.X.X., L.C., G.-Z.Z., S.V.P., and J.I.S.; methodology: X.W., L.C., I.L., D.W., and G.-Z.Z.; investigation: X.W., L.C., X.C., J.W., Y.C., and J.Z.; writing (original draft): X.W., J.X.X., and Z.X.; writing (review and editing): Z.X., J.X.X., L.C., J.I.S., S.V.P., D.W., G.-Z.Z., and X.W.; funding acquisition: Z.X.; visualization: X.W. and Z.X. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

Read the original here:
A caveolin binding motif in Na/K-ATPase is required for stem cell differentiation and organogenesis in mammals and C. elegans - Science Advances

Spinal Cord Stem Cells Comments Off on A caveolin binding motif in Na/K-ATPase is required for stem cell differentiation and organogenesis in mammals and C. elegans – Science Advances | May 27th, 2020

The impact of COVID-19 pandemic can be felt across the Healthcare Industry The growing inability in the production and manufacturing processes, in the light of the self-quarantined workforce has caused a major disruption in the supply chain across the sector. Restrictions encouraged by this pandemic are obstructing the production of essentials such as life-saving drugs.

The nature of operation in Pharmaceuticals plants that cannot be easily stopped and started, makes the operational restrictions in these plants a serious concern for the industry leaders. Restricted and delayed shipments from China have created a price hike in the raw materials, affecting the core of the Healthcare Industry.

Central nervous system comprises brain and spinal cord, and is responsible for integration of sensory information. Brain is the largest and one of the most complex organs in the human body. It is made up of 100 billion nerves that communicate with 100 trillion synapses. It is responsible for the thought and movement produced by the body. Spinal cord is connected to a section of brain known as brain stem and runs through the spinal canal. The brain processes and interprets sensory information sent from the spinal cord. Brain and spinal cord serve as the primary processing centers for the entire nervous system, and control the working of the body.

For detailed insights on enhancing your product footprint, request for a sample here @ https://www.persistencemarketresearch.com/samples/4160

Neuroprosthetics improves or replaces the function of the central nervous system. Neuroprosthetics, also known as neural prosthetics, are devices implanted in the body that stimulate the function of an organ or organ system that has failed due to disease or injury. It is a brain-computer interface device used to detect and translate neural activity into command sequences for prostheses. Its primary aim is to restore functionality in patients suffering from loss of motor control such as spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, and stroke. The major types of neuroprosthetics include sensory implants, motor prosthetics, and cognitive prosthetics. Motor prosthetics support the autonomous system and assist in the regulation or stimulation of affected motor functions.

Similarly, cognitive prosthetics restore the function of brain tissue loss in conditions such as paralysis, Parkinsons disease, traumatic brain injury, and speech deficit. Sensory implants pass information into the bodys sensory areas such as sight or hearing, and it is further classified as auditory (cochlear implant), visual, and spinal cord stimulator. Some key functions of neuroprosthetics include providing hearing, seeing, feeling abilities, pain relief, and restoring damaged brain cells. Cochlear implant is among the most popular neuroprosthetics. In addition, auditory brain stem implant is also a neuroprosthetic meant to improve hearing damage.

North America dominates the global market for neuroprosthetics due to the rising incidence of neurological diseases and growth in geriatric population in the region. Asia is expected to display a high growth rate in the next five years in the global neuroprosthetics market, with China and India being the fastest growing markets in the Asia-Pacific region. Among the key driving forces for the neuroprosthetics market in developing countries are the large pool of patients, increasing awareness about the disease, improving healthcare infrastructure, and rising government funding in the region.

For entire list of market players, request for TOC here @ https://www.persistencemarketresearch.com/toc/4160

Increasing prevalence of neurological diseases such as traumatic brain injury, stroke and Parkinsons disease, rise in geriatric population, increase in healthcare expenditure, growing awareness about healthcare, rapid progression of technology, and increasing number of initiatives by various governments and government associations are some key factors driving growth of the global neuroprosthetics market. However, factors such as high cost of devices, reimbursement issues, and adverse effects pose a major restraint to the growth of the global neuroprosthetics market.

Innovative self-charging neural implants that eliminate the need for high risk and costly surgery to replace the discharge battery and controlling machinery with thoughts would help to develop opportunities for the growth of the global neuroprosthetics market.

Pre-Book Right Now for Exclusive Analyst Support @ https://www.persistencemarketresearch.com/checkout/4160

The major companies operating in the global neuroprosthetics market are ,

Key geographies evaluated in this report are:

Key features of this report

Continue reading here:
Revenue from the Sales of Neuroprosthetics Market to Surge Exponentially Owing To High Demand During COVID-19 Lockdown and Forecast 2015 to 2021 -...

Spinal Cord Stem Cells Comments Off on Revenue from the Sales of Neuroprosthetics Market to Surge Exponentially Owing To High Demand During COVID-19 Lockdown and Forecast 2015 to 2021 -… | May 26th, 2020

However, stem cells could provide the answer to treating and repairing spinal cord injuries.

A British professor, Geoffrey Raisman, undertook research which showed that specific stem cells could enable a paralysed man to walk again.

He used stem cells called olfactory ensheathing cells (OECs) from the nose of a patient and transplanted them into the spinal cord. OECs are unique cells which are part of the sense of smell. They allow nerve fibres in the olfactory system to constantly regenerate. Prof Raisman proved that broken nerve fibres in the spinal cord could repair themselves by using OECs that were transplanted into the spinal cord of the patient. These specific stem cells (OECs) facilitated the growth of the ends of severed nerve fibres and caused them to join together.

A doctor in Portugal also transplanted olfactory stem cells to treat spinal cord injury in over 100 patients. These studies showed that a few patients were able to regain at least limited motor function and sensation after transplantation.

Although its early days, these studies show that neuronal type stem cells (NSCs) hold great promise to treat various neurodegenerative diseases and injuries to the spinal cord. Stem cells possess the ability to differentiate into many types of neural cell, depending upon their environment and the stimulus that is provided.

At present there are 55 clinical trials investigating the application of stem cells in spinal cord injury. These trials are studying various sources of stem cells including mesenchymal stem cells, bone marrow, umbilical cord tissue and adipose tissue derived stem cells.

(Marsala M, et.al. Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats. STEM CELLS Translational Medicine, 2019; 9 (2): 177 DOI: 10.1002/sctm.19-0156)

Please note: Stem cell therapy for spinal cord injury is in a research phase, and is not an established therapy.

Cord blood stem cell therapy for spinal cord injury is not available in South Africa.

Link:
Spinal Cord Injury And Stem Cells: New Perspectives ...

Spinal Cord Stem Cells Comments Off on Spinal Cord Injury And Stem Cells: New Perspectives … | May 21st, 2020

Spinal cord injury (SCI) involves damage to the area that can cause an impairment of loss of muscle control, movement and sensation. Currently, patients with injury to the spinal cord are managed with physical therapy, occupation therapy and other rehabilitation methods to cope with the physical changes.

However, stem cell research may present a new approach to the management of this patient group, ing for a potential improvement in the symptoms of the condition, such as incontinence, muscular control and sexual function.

Stem cells used in the treatment of SCI may come from various sources, including autologous mesenchymal CD34+ cells from own bone marrow, allogeneic mesenchymal cells from the human umbilical cord tissue or adipose tissue.

The bone marrow cells are taken from both hips of the patient, who is sedated with light general anesthetic. The cells are then tested for quality and bacterial contamination before they can be used in the research. Likewise, cells from umbilical cords are taken from healthy births and must pass rigorous screening prior to being passed for use in trials.

Scientific research conducted in animals with spinal cell injury has investigated the utility of stem cells in the repair of the injury. As a result of this research, a general understanding of the role that stem cells could play has been established. This includes:

Mesenchymal stem cells, also known as stromal stem cells, are a topic of interest in the research for treatment of spinal cord injury. The theory is for the stem cells to provide protection to and aid growth of the cells in the region of the injured spinal cord.

The safety and efficacy of different stem cell types have been investigated in several different studies. Various methods of administration have been trialed, including injection into the spine, the vein or the skin.

There has also been some research focused on embryonic stem cells in the management following spinal cord injury.

One study observed the effect of an injection of precursors of oligodendrocytes, to form the myelin sheath around the axons. However, after four patients were treated with the cells and observed for signs of restored nerve signaling, the study was discontinued. The belief that embryonic stem cells may be promising for spinal cord injury was not tainted.

Another study investigated the effect of hES cell-derived oligodendrocyte progenitor cells when injected into the site of thoracic spinal cord injury. Of five patients, none experienced serious side effects, and imaging tests revealed that the volume of injury was reduced in 80% of patients.

At this point in time, there is insufficient scientific evidence to recommend the used of stem cells for spinal cord injury as a routine practice. The technique is promising, however, offering the possibility of healing and the improvement of the symptoms, which is in contrast to the current practice that recommends coping mechanisms without a definitive cure or improvement.

For this reason, scientific research is likely to continue in the future in the hope of finding a suitable method to improve the quality of life for patients with spinal cord injury.

See the article here:
Stem cell research for spinal cord injury

Spinal Cord Stem Cells Comments Off on Stem cell research for spinal cord injury | May 21st, 2020

Coronavirus health scams are rampant, with businesses taking advantage of peoples fears to sell all sorts of unproven products for the prevention and treatment of COVID-19. Some of these snake oil cures are innocuous, such as elderberry juice, but others can be harmful, such as colloidal silver.

Among the products with considerable potential for harm are unproven stem cell therapies. Unfortunately, the emergence of this particular line of sham COVID-19 treatments isnt all that surprising. For more than a decade, businesses have been aggressively pitching unsubstantiated and unlicensed stem cell products to vulnerable and often desperate individuals with illnesses or injuries for which no known treatment exists, such as Alzheimers disease, amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD) and spinal cord injuries. The results have sometimes been deadly.

There are some medical conditions for which stem cell therapies have been shown to be safe and effective, but they are few in number mostly cancer and several blood and immune disorders.

Leigh Turner, a bioethicist at the University of Minnesota, has been investigating the direct-to-consumer marketing of spurious stem cell therapies and related exosome products in the United States for nearly a decade. In an article published recently in the journal Cell Stem Cell, Leigh describes the latest twist in this cynical saga: how some stem cell businesses are seizing the [COVID-19] pandemic as an opportunity to profit from hope and desperation.

MinnPost spoke with Turner late last week about what he found when researching that paper. The following is an edited transcript of the interview.

MinnPost: Companies seem to be using the same kind of marketing strategies to sell unproven stem cell therapies for COVID-19 as they have for other medical conditions.

Leigh Turner: Yes. These are opportunistic businesses. They look for marketplace opportunities, ways to generate e-revenue streams. And the COVID-19 pandemic is another business opportunity. Its not like theyve pivoted away from what they did in the past. If they were marketing stem cell treatments for Parkinsons disease, or ALS or spinal injuries, they havent stopped doing that. Theyve just added that theyve now got a stem cell treatment or an exosome therapy to treat or prevent COVID-19.

MP: They seem to be marketing their products primary as immune system boosters.

Leigh Turner

MP: At least one company is telling people that they should bank their stem cells to use as a treament if they get infected with the coronavirus.

LT: There are several business models at play right now. One is, come on in and get your stem cell immune booster to reduce your chances of getting COVID-19. They may also claim it will reduce your symptoms should you get it. Another marketing pitch is a bit more cautious. It says that if you come in now when youre in good health, they will bank your cells. Youll pay for the initial extraction of cells and also monthly or yearly for banking. The company then claims that should you fall ill with COVID-19 down the road, youll have those healthy cells available for you to use. Of course, they dont offer a lot of detail about how the cells would actually help you. You just supposed to take it for granted that they will.

MP: Theres no evidence of that.

LT: No. Its all just pseudoscience. But there is a meaningful hypothesis behind it. Thats how these businesses operate by fusing science with pseudoscience, credible research with junk claims.

MP: What is that hypothesis?

LT: There are companies and academic institutions right now that are interested in testing stem cell products, but not as immune boosters, not to prevent COVID-19 and not to eliminate the virus if someone gets infected. The studies right now are focusing on a very particular population of people with COVID-19 those who are typically in ICUs, suffering from acute respiratory distress syndrome. The hypothesis is that if certain types of stem cell products are administered to those people, we may be able to reduce inflammation in the lungs and help shorten the illness. But its a hypothesis.

MP: A good one?

LT: Its not an outrageous hypothesis. If you look at the existing literature, there have been studies done in the past that used stem cells for lung and respiratory disease. So far, those studies suggest that if you use clinical-grade stem cells and if you do it in a very rigorous way the safety profile is pretty good. But none of those studies has established extensive evidence of efficacy yet. Ideally, what you want is carefully designed, carefully conducted clinical trials testing that hypothesis and generating that evidence. These businesses the ones marketing stem cell therapies directly to individuals are not part of that scientific world.

MP: How do those businesses pull their customers in? How do they find them?

LT: They are typically big on social media. Im talking generally here, but they have Twitter accounts. They have YouTube channels. They have a Facebook page. Theyre not just putting up a website and hoping that somebody walks in the door. They hire social media marketing companies. They use marketing firms. They have pretty sophisticated marketing strategies that are tailored to particular demographics. It may be that they are targeting an elderly population, for example, because if youre interested in reaching people with COPD, youre not going to be trying to find 18-year-olds. Some businesses here in Minneapolis and elsewhere will have what they describe as educational seminars, which are basically infomercials. They are marketing events. They will try to get people to come to a convention center, a hotel [conference] room or a restaurant. Everything is free, but what theyll do is use hard-sell sales tactics to get people to commit, to write a check. Often theyll tell people that if they sign on today, theyll knock $2,000 or so off the price. But, of course, theyre not holding these events right now. They cant have these public gatherings.

MP: So, how are they selling people these products now, during the pandemic?

LT: More of it is happening online. One company, for example, uses a graduated pricing model. If its one person, its one price point. If its you and a family member, you both get a break on the procedure. And if its you and two additional family members, the price goes down even more. They use these things to try to get people to come in the door. One company in California has adapted to the pandemic in a different way. They have a do-it-yourself model. You dont have to even come into the clinic. You can buy their kit, and they ship it to your home. You then do the procedure at your dining room table.

MP: These stem cell products and treatments are quite expensive.

LT: Yes, some of the businesses Ive look at charge tens of thousands of dollars, although thats not necessarily for treating COVID-19. For COVID-19, it appears to be in the thousands-of-dollars category. In some cases, we dont know. The businesses can be pretty cagey. In some cases, they try to size up the customer and figure out how much they can extract from that person.

MP: Government agencies are cracking down on some of these stem cell businesses.

LT: The FDA (Food and Drug Administration), FTC (Federal Trade Commission) and Department of Justice have said that theyre going to be aggressive with dealing with these scams. And they have. Some businesses have already received letters from the regulators. That may be having a deterrent effect during the pandemic. Some businesses may want to jump in, but are afraid to do so. They may be waiting to see what happens before they take the chance.

MP: But the regulatory agencies are obviously not finding all of the businesses marketing unproven COVID-19 therapies.

LT: There is a lot of marketing fraud. And sometimes its quite challenging to figure out whats going on. Some of the clinics that I looked at didnt say, Were offering an immune booster for COVID-19. It was more just chatter. Clinics would put up a seven-minute video from one of their doctors about COVID-19 and emerging stem-cell research coming out of China, saying it was really encouraging. Then they would say, If you have any questions about stem cells and COVID-19, give us a call. So, whats the takeaway when a business does that? Does that mean they are selling stem cell treatments for COVID-19? Or are they just trying to get people to call? Its hard to know whats happening. If I had to guess, I say its a workaround. The businesses dont want to put it on their website, because thats too easy for someone from the FTC or the FDA to find. If they just put up a video, they can say theyre not marketing anything, that it was just meant to be educational.

MP: These businesses seem to rely on anecdotal cases or really small studies from China to support their claims.

LT: They use China in a couple of different ways. There was a case report, for example, that was published as a preprint. It wasnt published by a journal. It hasnt gone through peer review. It was just a preprint that someone put online. Its the case of a single individual with COVID-19 who received stem cells. Thats been written up in a very hyperbolic way, when really, its just a case report. Its one person. Some people get COVID-19 and recover anyway. You cant draw any conclusions from it about stem cells being efficacious, but its been written up that way. There was another study, very preliminary research, in which mesenchymal stem cells were administered to seven individuals with COVID-19 with various degrees of severity. A placebo was given to three individuals. The article doesnt provide the source of the stem cells. Nor does it provide much insight about the individuals who were given placebos, although they appear to be about 10 years older than [those receiving the stem cells]. It raises some interesting questions. It provides a basis for further research. But, unfortunately, some of the news media reports have been hyperbolic. Stem cell businesses use both these papers when marketing directly to consumers. They refer to these studies, and they also attach themselves to the bubbly media coverage.

MP: Consumers need to know that these products can be dangerous.

LT: Yes. The danger comes in several forms. Part of it is that these are financial scams lifting money off people who are worried and anxious. But, also, giving someone a product that hasnt been carefully tested in well-designed clinical trials raises a lot of concerns. Some businesses have released contaminated stem cell products into the marketplace. People end up getting infections and having to be hospitalized. It can be a very serious thing. Theres also the possibility that the wrong type of cell goes to the wrong part of the body and causes harm. When a company claims, for example, that a stem cell product will regenerate lung tissue and be an immune booster, one thing I would worry about is pulmonary embolisms. If someone is being given something that hasnt been thoroughly tested, its hard to know what would go wrong, but its easy to know something could go wrong.

FMI: Youll find the article on Cell Stem Cells website.

View original post here:
Unproven stem cell products are being peddled as COVID-19 'therapies,' U of M researcher reports - MinnPost

Spinal Cord Stem Cells Comments Off on Unproven stem cell products are being peddled as COVID-19 ‘therapies,’ U of M researcher reports – MinnPost | May 18th, 2020

Therapeutic Activities of Engrafted Neural Stem/Precursor Cells Are Not Dormant in the Chronically Injured Spinal Cord

From Stem Cells

Neural stem or precursor cells (NSPCs) have tremendous promise for use in cell-based therapies for the treatment of spinal cord injury (SCI) as they have been shown to provide trophic support following transplantation, allowing modification of the host environment to allow some endogenous regeneration and repair in animal models (Aboodyet al,Barnabe-Heider and Frisen, andMartino and Pluchino). However, few studies have assessed their role in the chronic phase of SCI (Tetzlaffet al) and any correlation to microenvironmental factors (Thuretet al), which is potentially important for the behaviour of transplanted NSPCs. Now, in a study published inStem Cellsfrom the laboratory of Seiji Okada at Kyushu University, Japan,Kumamaruet alcombine flow-cytometric isolation and RNA-Seq to analyse the transcriptome of NSPCs transplanted into SCI during the chronic phase, and have demonstrated that while the cells have a positive therapeutic effect, the refractory state of the chronically injured spinal cord hampers locomotory recovery.

To determine the chronic phase of SCI, a time course of the change in the number of inflammatory cells until 3 months after SCI was assessed. Neutrophil infiltration peaked at 12 hours and subsequently decreased, microglia increased and peaked at 6 weeks, while macrophages and monocytes first peaked at 12 hours and then again at 6 weeks. Gene expression analysis over the same time period found that levels of pro-inflammatory factors, anti-inflammatory factors, CXC chemokine ligands and CC chemokine ligands and growth and neurotrophic factors were very different between the acute (enriched in inflammatory cytokine/chemokines and neurotrophic factors) and the chronic (enriched in growth factors) stages of SCI. Next, Luciferase and GFP-labeled NSPCs were transplanted 3 months after SCI, where long-term cell viability was observed and graft survival rate of around 17% was observed at 42 days after transplantation. Transplanted NSPCs migrated up to 4mm rostrally or caudally from the graft site and had extended fine cellular processes. Chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of transplanted cell migration and survival and have been linked to transplant failure during the chronic phase (Karimi-Abdolrezaee et al). Analysis found that while CSPGs were abundant during the sub-acute phase of SCI, this reduced to normal levels at three months.

Subsequent RNA-Seq analysis of NSPCs analysed at 7 days after transplantation during the acute, sub-acute, and chronic phases of SCI found, as observed previously (Kumamaru et al), that transcriptional activity is reduced in NSPCs transplanted into the acutely injured spinal cord compared to those transplanted into nave spinal cords, however this reduction was not observed for the sub-acute and chronic phases, and increased transcriptional activity was observed in chronically transplanted NSPCs. Principal component analysis then suggested that sub-acutely injured spinal cords may promote the oligodendrocyte differentiation of transplanted NSPCs whereas chronically injured spinal cords promoted neuronal differentiation. Analysis of differentiation-associated gene expression found that chronically injured spinal cords were permissive for the differentiation of engrafted NSPCs with overexpressed genes representing neurogenesis and neuronal differentiation. Oligodendrocyte generation by engrafted NSPCs was not however inhibited in chronic SCI microenvironments but was more prominent in sub-acute SCI. Secreted molecules, which can act as trophic mediators, decreased markedly in acutely injured spinal cords but increased in chronically injured spinal cords. Finally, functional improvement was analysed and, while NSPC transplantation in the acute and sub-acute groups showed significantly improved functional recovery, the chronically NSPC-transplanted mice did not exhibit improved locomotor recovery.

Overall, this study shows that NSPCs which are transplanted into chronic phase SCI sites survive, are migratory, transcriptionally active, undergo neuronal and oligodendrocyte differentiation and secrete trophic factors at a level higher than expected from a refractory site, BUT, ultimately do not improve locomotor function. This suggests that the micro-environment of SCI in the chronic phase itself is the main barrier to the potential regenerative effects of NSPC transplantation. With this knowledge in hand, therapies for this type of injury will hopefully continue to evolve to a state where cell therapy and environmental modulation can work hand in hand to affect functional recovery.

References

FromStem Cells.

Stem CellCorrespondent Stuart P Atkinson reports on those studies appearing in current journals that are destined to make an impact on stem cell research and clinical studies.

See the rest here:
Spinal Cord Treatment Problems Site not the Cells ...

Spinal Cord Stem Cells Comments Off on Spinal Cord Treatment Problems Site not the Cells … | May 16th, 2020

Statements in this Quarterly Report that are not strictly historical areforward-looking statements and include statements about products in development,results and analyses of pre-clinical studies, clinical trials and studies,research and development expenses, cash expenditures, and alliances andpartnerships, among other matters. You can identify these forward-lookingstatements because they involve our expectations, intentions, beliefs, plans,projections, anticipations, or other characterizations of future events orcircumstances. These forward-looking statements are not guarantees of futureperformance and are subject to risks and uncertainties that may cause actualresults to differ materially from those in the forward-looking statements as aresult of any number of factors. These factors include, but are not limited to,risks relating to our: ability to conduct and obtain successful results fromongoing pre-clinical and clinical trials, commercialize our technology, obtainregulatory approval for our product candidates, contract with third parties toadequately test and manufacture our proposed therapeutic products, protect ourintellectual property rights and obtain additional financing to continue ouroperations. Some of these factors are more fully discussed, as are otherfactors, in our Annual Report on Form 10-K for the fiscal year ended December31, 2019, as filed with the SEC, in our subsequent filings with the SEC as wellas in the section of this Quarterly Report entitled "Risk Factors" and elsewhereherein. We do not undertake to update any of these forward-looking statements orto announce the results of any revisions to these forward-looking statementsexcept as required by law.We urge you to read this entire Quarterly Report on Form 10-Q, including the"Risk Factors" section, the condensed consolidated financial statements, andrelated notes. As used in this Quarterly Report, unless the context otherwiserequires, the words "we," "us," "our," "the Company" and "Seneca" refers toSeneca Biopharma, Inc. and its subsidiary. Also, any reference to "commonshares" or "common stock," refers to our $.01 par value common stock. Anyreference to "Series A Preferred Stock" or "Preferred Stock" refers to ourSeries A 4.5% Convertible Preferred Stock. The information contained herein iscurrent as of the date of this Quarterly Report (March 31, 2020), unless anotherdate is specified. On July 17, 2019, we completed a 1-for-20 reverse stock splitof our common stock. All share and per shares information in this report havebeen adjusted to reflect the reverse stock split. We prepare our interimfinancial statements in accordance with U.S. GAAP. Our financials and results ofoperations for the three-month period ended March 31, 2020 are not necessarilyindicative of our prospective financial condition and results of operations forthe pending full fiscal year ending December 31, 2020. The interim financialstatements presented in this Quarterly Report as well as other informationrelating to our Company contained in this Quarterly Report should be read inconjunction and together with the reports, statements and information filed byus with the SEC.Our Management's Discussion and Analysis of Financial Condition and Results ofOperations or MD&A is provided, in addition to the accompanying condensedconsolidated financial statements and notes, to assist you in understanding ourresults of operations, financial condition and cash flows. Our MD&A is organizedas follows:

Executive Overview - Discussion of our business and overall analysis of

financial and other items affecting the Company in order to provide context for

Trends & Outlook - Discussion of what we view as the overall trends affecting

Critical Accounting Policies - Accounting policies that we believe are

important to understanding the assumptions and judgments incorporated in our

Results of Operations - Analysis of our financial results comparing the

three-month periods ended March 31, 2020 to the comparable period of 2019.

Liquidity and Capital Resources - An analysis of cash flows and discussion of

Our patented technology platform has three core components:

1. Over 300 lines of human, regionally specific neural stem cells, some of which

have the potential to be used to treat serious or life-threatening diseases

through direct transplantation into the central nervous system;

2. Proprietary screening capability - our ability to generate human neural stem

cell lines provides a platform for chemical screening and discovery of novel

compounds against nervous system disorders; and

3. Small molecules that resulted from Seneca's neurogenesis screening platform

To date, our technology platform has produced two lead assets in clinicaldevelopment: our NSI-566 stem cell therapy program and our NSI-189 smallmolecule program. A component of our current strategy is out-licensing and wehave recently initiated a formal out-licensing initiative aimed at securingpartners to advance the clinical development of these two programs.

In-licensing and Acquisition Strategy

Below is a description of our clinical programs, their intended indication andcurrent stage of development:

Motor Deficits Due to Ischemic Stroke

Amyotrophic Lateral Sclerosis

Chronic Spinal Cord Injury

Clinical Experience with NSI-566

Amyotrophic Lateral Sclerosis

Pre-Clinical Experience with NSI-566 and other candidates in our stem cellpipeline

NSI-189 (Small Molecule Pharmaceutical Compound)

Major Depressive Disorder (MDD)

Clinical Experience with NSI-189

Preclinical Experience with NSI-189

NSI-189 has shown promise in preclinical studies evaluating its impact in animalmodels for a number of different disease indications, including:

1. Ischemic stroke-in 2017 Tajiri and colleagues published a manuscript

reporting that NSI-189 ameliorated motor and neurological deficits in a

rodent model of ischemic stroke (Tajiri et al., J Cell Physiol 2017,

232(10):2731-2740)

2. Radiation-induced cognitive dysfunction-in 2018 Allen and colleagues

published a manuscript reporting that NSI-189 treatment could reverse

cognitive deficits in rats caused by cranial irradiation, a model of cranial

radiotherapy in the treatment of brain tumors (Allen et al., Radiat Res 2018,

189(4):345-353).

3. Angelman syndrome-in 2019 Liu and colleagues published a manuscript reporting

that NSI-189 reversed impairments in cognitive and motor deficits in a rodent

model of Angelman syndrome and increased synaptic strength in sections of

brains taken from these animals (Liu et al., Neuropharmacology 2019,

144:337-344). Angelman syndrome (AS) is a rare congenital genetic disorder

caused by a lack of function in the UBE3A gene on the maternal 15th

chromosome. It affects approximately one in 15,000 people - about 500,000

individuals globally. Symptoms of AS include developmental delay, lack of

speech, seizures, and walking and balance disorders.

4. Diabetes-associated peripheral neuropathy-in 2019 Jolivalt and colleagues

published a manuscript reporting that NSI-189 mitigated or reversed

disease-associated central and peripheral neuropathy in two rodent models of

diabetes (Jolivalt et al., Diabetes 2019, (11):2143-2154). Improvements

resulting from NSI-189 treatment were seen on multiple sensory and cognitive

Our Proprietary and Novel Screening Platform

Small Molecule Pharmaceutical Compounds.

In addition to patenting our technologies, we also rely on confidential andproprietary information and take active measures to control access to thatinformation, including the use of confidentiality agreements with our employees,consultants and certain of our contractors.

As of April 30, 2020, we had seven (7) full-time employees. We also use theservices of several outside consultants in business and scientific matters.

We generated no revenues from the sale of our proposed therapies for any of theperiods presented.

We have historically generated minimal revenue from the licensing of ourintellectual property to third parties as well as payments under a settlementagreement.

Research and Development Expenses

We have a wholly-owned subsidiary in the People's Republic of China thatprimarily oversees our current clinical trial to treat motor deficits due toischemic stroke.

General and Administrative Expenses

Comparison of Three Months Ended March 31, 2020 and 2019

Revenue

Operating expenses for the three months ended March 30 were as follows:

Research and Development Expenses

General and Administrative Expenses

Other income (expense)

Other expense, net totaled approximately ($5,585,000) and ($657,000) for thethree months ended March 31, 2020 and 2019, respectively.

Cash Flows - 2020 compared to 2019

Net cash used in operating activities $ (1,677,629 )$ (1,665,905 )$ (11,724 )

Net cash provided by financing activities $ 6,593,428$ (117,019 )$ 6,710,447

Net Cash Used in Operating Activities

Net Cash (Used in) Provided by Investing Activities

There were no investing activities in either of the three months ended March 31,2020 or 2019.

Net Cash Used in by Financing Activities

Edgar Online, source Glimpses

Read this article:
SENECA BIOPHARMA : MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-Q) - marketscreener.com

Spinal Cord Stem Cells Comments Off on SENECA BIOPHARMA : MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-Q) – marketscreener.com | May 16th, 2020

CAMBRIDGE, Mass.--(BUSINESS WIRE)--QurAlis Corporation, a biotech company focused on developing precision therapeutics for amyotrophic lateral sclerosis (ALS) and other neurologic diseases, today announced the raise of a $42 million Series A financing, bringing the total funds raised to $50.5 million. The financing was led by LS Polaris Innovation Fund, lead seed investor Mission BioCapital, INKEF Capital and the Dementia Discovery Fund, and co-led by Droia Ventures. Additional new investors include Mitsui Global Investment and Dolby Family Ventures, joined by investments from existing investors Amgen Ventures, MP Healthcare Venture Management, and Sanford Biosciences. QurAlis intends to use this funding to support the development of new therapies for ALS and genetically related frontotemporal dementia (FTD), neurodegenerative diseases for which there is currently no cure.

This Series A funding will allow us to take the next major step in our growth and advance our lead programs into the clinic. Recent advances in science and technology have identified strong disease targets for specific groups of ALS and FTD patients. Combined with our proprietary human stem cell technologies and development capabilities, we believe we are placed in a very good position to bring forth real treatments, said Kasper Roet, Ph.D., Chief Executive Officer of QurAlis. The QurAlis team built this company from the ground up on a foundation of cutting-edge science and profound dedication to helping ALS patients above all else. The great support of our existing and new investors from the US, Europe and Japan underscores the international nature of our mission. We plan to use this funding to continue advancing ALS and FTD therapies for patients around the world who are in critical need of effective treatments.

As ALS can be caused by mutations in over 25 individual human genes, many of which also cause FTD, QurAlis strategy is to systematically investigate treatments targeting specific disease-causing mechanisms in patient sub-populations. The company evaluates a wide range of potential treatments through the companys transformative system that utilizes lab-grown neuronal networks derived from cells of ALS patients.

Between the companys strong scientific foundation and support by ALS luminaries Kevin Eggan and his co-founders, promising pipeline of potential ALS treatments, and its dedicated team of experts in the field of neurologic therapeutics, QurAlis is very well positioned to make a tremendous difference for patients with ALS and FTD, said Amy Schulman, Managing Partner of the LS Polaris Innovation Fund. We are proud to support their mission and have deep faith in their transformative technology, which has already supported the discovery of several promising ALS candidate therapeutics.

In connection with the financing round, Amy Schulman, Managing Partner of the LS Polaris Innovation Fund; Roel Bulthuis, Managing Partner at INKEF Capital; Jonathan Behr, Ph.D., Partner at the Dementia Discovery Fund; and Luc Dochez, Managing Partner at DROIA Ventures, will be joining Johannes Fruehauf, M.D., Ph.D., General Partner at Mission BioCapital, on QurAlis Board.

About ALS

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrigs disease, is a progressive neurodegenerative disease impacting nerve cells in the brain and spinal cord. ALS breaks down nerve cells, reducing muscle function and causing loss of muscle control. ALS can be traced to mutations in over 25 different genes and is often caused by a combination of multiple sub-forms of the condition. Its average life expectancy is three years, and there is currently no cure for the disease.

About QurAlis Corporation

QurAlis is developing precision therapeutics for ALS, a terminal disease that causes muscle paralysis through degeneration of the motor system. We are digging deep into the root causes of the multiple sub-forms of this destructive disease and focus our programs on tackling specific disease-causing mechanisms.

The rest is here:
QurAlis raises $42 Million Series A Financing to Develop New Therapies for Amyotrophic Lateral Sclerosis (ALS) - Business Wire

Spinal Cord Stem Cells Comments Off on QurAlis raises $42 Million Series A Financing to Develop New Therapies for Amyotrophic Lateral Sclerosis (ALS) – Business Wire | May 16th, 2020

Spinal Cord Trauma Treatment Market: Global Industry Analysis 2012 2016 and Forecast 2017 2025is the recent report of Persistence Market Research that throws light on the overall market scenario during the period of eight years, i.e. 2017-2025. According to this report, Globalspinal cord trauma treatment marketis expected to witness significant growth during the forecast period.

This growth is expected to be primarily driven by increasing incidence of spinal cord trauma, and increasing government support to reduce the burden of spinal cord injuries. Additionally, development of nerve cells growth therapy is expected to boost the market in near future.

Report To Be Covered

Sales Revenue:Market Share, Growth Rate, Current Market Analysis.Product Revenue for Top Players: Market Share, Growth Rate, Current Market Situation Analysis.Industry Trends: United States and Other Regions Revenue, Status and Outlook.Market Segment: By Types, By Applications, By Regions/ Geography.Market Environment: Government Policies, Technological Changes, Market Risks.Market Drivers: Growing Demand, Reduction in Cost, Market Opportunities and Challenges.Competitive Landscape: By Manufacturers, Development Trends, Marketing Area

Get Sample Copy of Report @https://www.persistencemarketresearch.com/samples/17353

Company Profiles

Get To Know Methodology of Report @https://www.persistencemarketresearch.com/methodology/17353

The global market for spinal cord trauma treatment is is estimated to be valued atUS$ 2,276.3 Mnin terms of value by the end of 2017. The global spinal cord trauma treatment market is expected to expand at aCAGR of 3.7%over the forecast period to reach a value ofUS$ 3,036.2 Mnby 2025end.

Global Spinal Cord Trauma Treatment Market: Trends

Global Spinal Cord Trauma Treatment Market: Forecast by End User

On the basis of end user, the global spinal cord trauma treatment market is segmented into hospitals and trauma centers. Hospitals segment dominated the global spinal cord trauma treatment market in revenue terms in 2016 and is projected to continue to do so throughout the forecast period.

Hospitals and trauma centers segments are expected to approximately similar attractive index. Hospitals segment accounted for53.2%value share in 2017 and is projected to account for52.5%share by 2025 end.

Access Full Report @https://www.persistencemarketresearch.com/checkout/17353

Explore Extensive Coverage of PMR`sLife Sciences & Transformational HealthLandscape

Proton Therapy Systems Market

Proton Therapy Market Segmented By Single Room, Multiple Room Set up Type with Head and Neck Cancer, Brain Cancer, Sarcoma Pediatric Cancer, Gastro-intestinal Cancer, Prostate Cancer, Lung Cancer Indication.For More Information

Trauma Fixation Devices Marketglobal trauma fixation devices market is estimated to represent more than US$ 450 Mn of the total market in 2017 and is estimated to reach little more than US$ 800 Mn by 2025 end, expanding at CAGR of 7.5% over the forecast period of 20172025.For More Information

About us:

Persistence Market Research (PMR) is a third-platform research firm. Our research model is a unique collaboration of data analytics andmarket research methodologyto help businesses achieve optimal performance.

To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

Our client success stories feature a range of clients from Fortune 500 companies to fast-growing startups. PMRs collaborative environment is committed to building industry-specific solutions by transforming data from multiple streams into a strategic asset.

Contact us:

Ashish KoltePersistence Market ResearchAddress 305 Broadway, 7th FloorNew York City,NY 10007 United StatesU.S. Ph. +1-646-568-7751USA-Canada Toll-free +1 800-961-0353Sales[emailprotected]Websitehttps://www.persistencemarketresearch.com

Read the original:
PMR : Spinal Cord Trauma Treatment Market Worth Will Reach US$ 3000 Mn According To Forecast By 2025 - Cole of Duty

Spinal Cord Stem Cells Comments Off on PMR : Spinal Cord Trauma Treatment Market Worth Will Reach US$ 3000 Mn According To Forecast By 2025 – Cole of Duty | May 14th, 2020

Stem cells have long-held hope for many people with spinal cord injuries. Since their discovery in 1998, they have been used in thousands of studies to one day cure paralysis, but there is still no cure for those with chronic injuries. Despite this, scientists have come a long way, especially in recent years. You have likely heard about some of the research in the news, stirring more hope than ever before.

And the hope is not unfounded. The hard work and the millions of dollars going into this research is finally seeing results. Stem cells may not be the only key to finding a cure for a spinal cord injury, but they arent going anywhere and are being used in hundreds of studies around the world. Here are the ones you should know about.

The human body has millions of stem cells that can be found all over the body. Researchers at the Mayo Clinic were recently in the news for their results using fat-derived adult stem cells from the patients own body. This study recruited 10 individuals with traumatic spinal cord injuries. Each was injected with stem cells taken from the fat in their stomachs and was expanded in the lab for eight weeks. The injection was then in the lower lumbar area.

This treatment is brand new and has not been approved by the FDA, however, the study was granted special clearance. One individual in the study, a man in his fifties with an incomplete injury who had leg return and was able to walk slightly post-injury without treatment, saw a nearly 50% increase in his abilities after receiving the injection.

Researchers also made sure to wait until each person in the study had plateaued after their injuries to be sure that the results from the treatment were not results from the body still having a new injury. There is currently no further news on whether the FDA will approve this treatment for the general population.

Nearly a year ago, Japan's Health Ministry approved a trial that will involve four people with complete injuries. This stem cell trial uses induced pluripotent stem cells (IPS) taken from embryos and will be grown into two million nerve cells for each patient. These cells will then be injected into the injury site. This trial comes from Masaya Nakamura, a professor at Okano and Keio University, who saw improvements in animals after they underwent the procedure. There has that no updates on this trial since it was approved.

In Spain, a clinical trial has been underway for the last few years that uses stem cells taken from the patient's bone marrow and injected into their injury site. This research comes from Dr. Vaquero at the Puerta de Hierro University Hospital in Spain. His first trial in 2016 included people with complete injuries and his second trial in 2017 included people with incomplete injuries. Almost all patients who underwent the procedure saw some improvement, with some seeing more improvement than others. The trial is currently seeking 30 people with incomplete injuries for its next phase.

Dr. Steven Levy of MD Stem Cells is launching the SciExVR trial using a patient's stem cells from their bone marrow as well. This study is currently recruiting patients in the United States and will involve exoskeleton rehab as part of the trial. Learn more:http://mdstemcells.com/sciexvr

Dr. Wise Young, along with Rutgers University and his organization SCINetChina, has been approved for a study in the United States that will involve umbilical cord blood stem cells and oral lithium. This study will involve 27 people with complete chronic injuries levels C5-T11. You must be able to be in New Jersey for six months is chosen.

Six years ago in 2014, Dr. Raisman from Poland pioneered a study using nerve stem cells taken from the nose. These stem cells were taken from the olfactory bulb deep in the brain and were transplanted into the injury site along with nerve tissue taken from the patient ankle. This study is recruiting one person for the trial who has a perfectly severed spinal cord (by a knife or similar). The person recruited will also have to spend several years in Poland. To learn more, contacthttps://walk-again-project.org/#/en

Keep in mind that all the above stem cell trials are still trials and that they cannot promise any return of movement or sensation. It is always in your best interest to go into a trial with an open mind and to be hopeful, but be realistic at all times.

Read more from the original source:
The Latest In Stem Cell Therapy After SCI

Spinal Cord Stem Cells Comments Off on The Latest In Stem Cell Therapy After SCI | May 13th, 2020

Bioscience Americas and the Global Institute of Stem Cell Therapy and Research would like to extend a special thank you to the Christopher and Dana Reeve Foundation for their support relating to our work at the University California Irvin and the Anderson Laboratory. We have made exciting progress using stem cells to treat cervical spinal cord injuries because of their generosity.

Now, based on the results of Dr. Andersons Phase I/II clinical trial, our research partners are conducting a Phase II proof of concept trial using HuCNS-SC in cervical spinal cord injury. In this study, research participants are being treated between 10 to 23 months post-injury.

Spinal Cord Injury (SCI) is damage to the human spinal cord into three different segments of the neural tissue leading to a severe form of motor and sensory loss. The kind of damage can be differentiated as:

In most of the reported cases of SCI, damage can be due to trauma or disease. Apart from the physical damage and complete dependency on caregivers, SCI can be emotionally damaging as well. Due to dependency even on basic mobility, negative attitudes of suffering trauma forever and frequent mood swings can lead suffers to remove themselves from social participation. Thus more than 30% of the reported cases of SCI showed significant signs of depression and negative impact on the functional improvement of overall health.

How prevalent is SCI?

Since SCI is associated with the loss of mobility, paralysis, and mortality due to other opportunistic infections, it is known as one of the most critical and disastrous medical conditions. Every year around 2 million to 5 million people are reported to suffer from spinal cord injury. On an average, middle-aged and young adult males are more susceptible to SCI mainly due to avoidable causes such as road accidents, injury, falls or violence. Mortality associated with SCI has been observed to be the highest immediately after the injury than in later years. The risk of mortality doubles with the severity level and is observed to be strongly influenced by the immediate availability of the best medical care. Preventable secondary opportunistic infections are also reported to be a major cause of death in many SCI patients, especially in the lower income groups.

About 90% of patients in the age group of 20-45 have been reported to face other complications such as limited employment, decreased quality of life, and severe depression.

Factors responsible for SCI.

In general, a spinal cord injury is a result of to the severe damage to different parts of the spinal cord such as the vertebral column, ligaments or the spinal disks. This typically originates from sudden trauma to the spinal cord such as fracturing, crushing or dislocating one or more vertebrae. Additional damage has been reported due to excessive bleeding, swelling, inflammation as well as other opportunistic infections. The most common reported causes of Spinal Cord Injury are:

Symptoms Associated with SCI

In general, the severity, as well as the area of injury, are the factors to be of concern in most of the cases of Spinal Cord Injury. On the basis of severity of injury, SCI is classified as:

What goes wrong in Spinal Cord Injury?

The human spinal cord is a fragile bridge connecting the brain to the other organs of the body. The spinal cord is encased in a protective covering of spinal vertebrae of the spinal column to prevent its damage from shock or injury. Our central nervous system, i.e., brain and spinal cord, is made up of millions of cells which coordinate and communicate to pass on the information from the brain to the other organs of the body via the spinal cord. This information is passed in the form of electrical signals which are then decoded by the specific organ.

Each neuron is made up of a cellular body with a long slender projection called the nerve fiber. These fibers are attached to other fibers to form a dense network of cells. In general, neurons carrying messages down the cord from the brain to other organs of the body are known as Motor Neurons. These neurons control the muscles of some of the important internal organs of the body such as heart, stomach, intestine, etc. The neurons traveling up the cord to the brain are known as Sensory Neurons, carrying sensory information from skin, joints, and muscles to control our ability to sense, touch and regularize temperature.

These neurons are insulated from the outer side by the coating of Oligodendrocytes and myelin sheath. These cells insulate the neuron to protect them from sudden damage and shock.

If any of the above types of cells are affected due to sudden damage such as shearing, laceration, stretching or shock, then the network of cells is disturbed due to which the passage of information from the brain to the spinal cord and vice versa is halted.

How Stem Cells treatment can help.

Stem cells are the mother cells that are responsible for developing an entire human body from tiny two-celled embryos. Due to their unlimited divisions and strong power to differentiate into all the cells of different lineage, the power of stem cells has been harnessed by our technology to isolate them outside the human body, concentrate in a clean environment, and implant back.

Thus stem cells treatment involves administration of concentrated cells in the targeted area, wherein they can colonize in the damaged area, adapt the properties of resident stem cells and initiate some of the lost functions that have been compromised by the disease or injury.

Thus with our standardized, broad-based and holistic approach, it is now possible to obtain noticeable improvements in SCI cases, in the symptoms as well as their functional abilities.

Continue reading here:
Spinal Cord Injury Recovery Through Stem Cell Therapy

Spinal Cord Stem Cells Comments Off on Spinal Cord Injury Recovery Through Stem Cell Therapy | May 13th, 2020

They hold huge promise, but stem cell-based spinal cord treatments wont be clinically available in the near future

My three-year-old son was born with a very large spinal lipoma. He was considered quadriplegic. Through conventional physical and occupational therapies and surgery to remove some of the lipoma he has gained enough function to walk with a walker and use his arms. However, he is experiencing some regression as his nerves are dying.

I have saved the cord blood from his younger brother and sister. New research where mice are being paralyzed and then injected with stem cells looks very promising to us. The mice nerves that are sick or weak are being protected and strengthened. Our son needs his nerves protected from degeneration.

Conventional surgery is no longer an option because the nerve roots travel in and out of the lipoma and cannot be separated from the lipoma. Our only hope is to protect and strengthen what function he currently has.

My question is: How long before this type of stem cell therapy will be used on humans, more specifically children? And how do we get to be first in line? If it is 10 or 20 years away, there may be no way to save the function our son has worked so hard to gain. I havent read anything about risks or side effects. There have to be some, what are they? Also, are there other countries that are more aggressive in their use of stem cells on humans for treating paralysis resulting from spinal cord injury?

Barbara BourgeoisCentreville, Virginia, USA

There isnt an easy answer here, and Im not clear as to why function is being lost at this pointin particular, whether the lipoma is recurring. If this is the case, resolution of the lipoma is the main issue. In some instances, it is impossible to completely remove the tumor, severely limiting the potential benefits of secondary therapeutics (such as stem cells). However, on the topic of stem cells in particular, there are several issues to discuss.

First, there are many sources of stem cells, and this affects their potential clinical use. Cord blood-derived stem cells are probably the farthest away from potential clinical use for spinal cord injury at this point, because there has been less basic research done with them so far. Human embryonic and adult stem cell lines may be somewhat closer, but research on these in the laboratory has been somewhat mixedsome very promising results with regaining motor function, and some big potential concerns, such as causing tumor formation.

As a result, we are most likely still years away from testing these treatments in patients, even to establish safety. Some other kinds of cell treatments, such as ensheathing glial cells, are being tried in the clinic in China, Russia and Portugal based on previous laboratory research in the US. However, none of these overseas trials has been designed in accordance with US standards to rigorously test safety and efficacy, and it is very difficult to evaluate the patchy data coming out so far.

To sum up, as a researcher, I think stem cells hold a huge amount of promise, but we arent yet at a point where this work will be translated to the clinic in the immediate future.

Answered by Aileen J. Anderson ~ 1/22/2004

Posted on January 27th, 2004 in General SCI and Human Interest. Tagged: stem cells

Go here to see the original:
When Will Stem Cells Heal Spinal Cord Damage?

Spinal Cord Stem Cells Comments Off on When Will Stem Cells Heal Spinal Cord Damage? | May 13th, 2020

Akin to cystic fibrosis (CF), scientists understand that certain mutations contribute to the development of the fatal neurological disorder amyotrophic lateral sclerosis (ALS). And much like CF drugmaker Vertex, a small Cambridge, Massachusetts-based biotech is forging a path to engineering precision therapies to treat the disease that killed visionary physicist Stephen Hawking.

The company, christened QurAlis, now has $42 million in its coffers with three preclinical programs and 5 employees (including senior management) to combat an illness that has long flummoxed researchers, resulting in a couple of approved therapies over the course of decades, neither of which attacks the underlying cause of the rare progressive condition that attacks nerve cells located in the brain and spinal cord responsible for controlling voluntary muscles.

ALS garnered international attention when New York Yankees player Lou Gehrig abruptly retired from baseball in 1939, after being diagnosed with the disease. In 2014, ALS returned to the spotlight with the Ice Bucket Challenge, which involved people pouring ice-cold water over their heads, posting a video on social media, and donating funds for research on the condition.

QurAlis chief Kasper Roet, whose interest in ALS was piqued while he was working on his PhD at the Netherlands Institute for Neuroscience focusing on a treatment for spinal cord paralysis and moonlighting at the Netherlands Brain Bank as an ad-hoc autopsy team coordinator, saw an opportunity to combat ALS when Harvard scientists Kevin Eggan and Clifford Woolf pioneered some new stem cell technology.

Essentially, they found a way to take skin cells from a patient, turn them into stem cells, and turn those into the nerve cells that are degenerating. Thats the missing link, Roet said. So now we can finally use patients own cells to both do target discovery and develop potential therapeutics.

So Roet packed up his things and shifted base to Boston to learn more, with plans to head back to Europe to start a company. He never left. QurAlis was born in 2016, working out of a co-working space called LabCentral after winning a spot via an Amgen-sponsored innovation competition. The company was carved out of a collaboration with Eggans startup Q-State Biosciences, which developed laser technology to examine cell behavior examining how a neuron fires was imperative in the drug discovery process for ALS.

QurAlis, which counts Vertexs founding scientist Manuel Navia as an advisor, now has three preclinical programs. The furthest along is a therapy designed to target a specific potassium channel that is implicated in certain ALS patients the plan is to take that small molecule into the clinic next year, Roet said.

It has become really clear that if you understand why a specific tumor is developing you can develop very specific targeted therapies, he explained in an interview drawing a parallel between ALS and oncology. Thats exactly the same strategy that we are following for ALS. The genetics have shown that over 25 genes are causing the (ALS) mutations. Some of them work together, some of them are very dominant and work alone what we are doing is trying to get those specific proteins that are tied to very specific ALS populations, where we know that that specific target plays a very important and crucial role in the development of the disease.

In 2018, QurAlis scored seed funding from Amgen, Alexandria, and MP Healthcare Venture Management. The Series A injection was led by LS Polaris Innovation Fund, lead seed investor Mission BioCapital, INKEF Capital and the Dementia Discovery Fund, and co-led by Droia Ventures. Additional new investors include Mitsui Global Investment and Dolby Family Ventures, and existing investors Amgen Ventures, MP Healthcare Venture Management, and Sanford Biosciences also chipped in.

Roet is not sure how long these funds will last, particularly given the uncertainty of the coronavirus pandemic. But some of the capital will be used in hiring, given that the QurAlis team is comprised of a mere five people, including Roet.

Weve been very productive, he said. But we can definitely use some extra hands.

Read more:
Precision therapy approach secures small biotech $42M haul to combat disease that inspired the Ice Bucket Challenge - Endpoints News

Spinal Cord Stem Cells Comments Off on Precision therapy approach secures small biotech $42M haul to combat disease that inspired the Ice Bucket Challenge – Endpoints News | May 13th, 2020