Atlanta pilot with an aggressive cancer finds lifesaving help from a stranger and a simple test   The Atlanta Journal Constitution

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scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes  Nature.com

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You are the match. How UNC student honored her late grandfather with life-saving effort  Raleigh News & Observer

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Researchers have brought the promise of stem cell therapies closer to reality  The Week

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Abstract

Extensive research has explored the functional correlation between stem cells and progenitor cells, particularly in blood. Hematopoietic stem cells (HSCs) can self-renew and regenerate tissues within the bone marrow, while stromal cells regulate tissue function. Recent studies have validated the role of mammalian stem cells within specific environments, providing initial empirical proof of this functional phenomenon. The interaction between bone and blood has always been vital to the function of the human body. It was initially proposed that during evolution, mammalian stem cells formed a complex relationship with the surrounding microenvironment, known as the niche. Researchers are currently debating the significance of molecular-level data to identify individual stromal cell types due to incomplete stromal cell mapping. Obtaining these data can help determine the specific activities of HSCs in bone marrow. This review summarizes key topics from previous studies on HSCs and their environment, discussing current and developing concepts related to HSCs and their niche in the bone marrow.

Keywords: hematopoietic stem cells, hematopoietic progenitor cells, bone marrow microenvironment, niche

Blood is a bodily fluid that delivers oxygen and nutrients to cells while collecting and transporting carbon dioxide and waste products produced by cellular metabolism [1]. Blood consists of plasma (a liquid component), red blood cells, white blood cells, and platelets. Hematopoiesis is the biological process through which blood and immune cells are produced [2] (Figure 1). Hematopoietic stem cells (HSCs) in the bone marrow are responsible for continuously replenishing these cells due to their limited lifespan [3]. HSCs occupy the highest position in the hierarchy of hematopoietic cells. The HSC niche in bone marrow is a specialized microenvironment that regulates the maintenance and activity of HSCs [4]. This niche governs self-renewal and differentiation of HSCs, ensuring the continual maintenance of hematopoiesis [5]. The bone marrow microenvironment was first introduced as a niche for HSCs in the 1970s [6]. The niche supplies the necessary components for the self-renewal and differentiation of HSCs. Additionally, the niche controls the states of rest and progression at various stages of the cell cycle in stem cells [6] (Figure 2). It also communicates crucial information to stem cells regarding the surrounding tissue, influences the development of stem cell offspring, and helps prevent genetic mutations [7]. Numerous studies have revealed the significance of HSCs and their niche, leading to a better understanding of their relationship [7,8,9,10,11].

Hematopoietic stem cell (HSC) regulation in steady-state and hematological malignancies. This image shows the features of HSC regulation between normal conditions and hematological malignancy. In normal hematopoiesis, HSCs are activated in response to signals from the bone marrow microenvironment. Upon activation, HSCs undergo proliferation to increase their numbers and develop into multipotent progenitors (MPPs). MMPs can evolve into more committed lymphoid/myeloid progenitors and their respective sub-progenitors (e.g., GMP, MEP, etc.). These progenitor cells undergo further differentiation and maturation to give rise to the diverse range of blood cell types found in circulation. Each cell in the hematopoietic process can be distinguished by differentiation markers. This tightly regulated process of activation, proliferation, and differentiation ensures the continuous replenishment of blood cells to maintain homeostasis. When the HSCs and the progenitors within the developing HSCs become damaged, they can transform into leukemic stem cells (LSCs). LSCs possess self-renewal capabilities and aberrant differentiation, giving rise to leukemic blasts that result in leukemia. CLP: Common lymphoid progenitor. CMP: Common myeloid progenitor. GMP: GranulocyteMacrophage progenitor. MEP: Megakaryocyteerythrocyte progenitor. Pro-B: Progenitor cell-B. Pro-T: Progenitor cell-T. Pro-NK: Progenitor cell-NK. Pro-DC: Dendritic progenitor cell. MncP: Monocyte progenitor. GrP: Granulocytic progenitor. EryP: Erythrocytic progenitor. MkP: Megakaryocyte progenitor. NK cells: Natural killer cells.

An image showing bone marrow microenvironment with their components. It shows two BM niches, two bone marrow niches, and the endosteal and vascular niches. The endosteal niche and vascular niche are two crucial microenvironments within the BM. The endosteal niche, located near the bone surface, provides a specialized environment for hematopoietic stem cells (HSCs) to reside and self-renew. The osteoblast is considered the most important cell in the endosteal niche; hence, it is also referred to as the osteoblastic niche. In contrast, the vascular niche, adjacent to blood vessels, supports HSCs by supplying nutrients and signaling molecules necessary for their proliferation and differentiation. It is composed of endothelial cells lining the blood vessels, as well as pericytes and smooth muscle cells surrounding them. Together, these niches play integral roles in regulating the maintenance and function of HSCs in the bone marrow. CAR cell: CXCL12-abundant reticular cell. OPN: Osteopontin. ANG1: Angiopoietin-1, SCF: Stem cell factor.

Due to global advancements in aging research and the increase in life expectancy over the past 150 years, studies on the physiological changes that occur in organisms as they age have made substantial progress [12,13]. Aging is characterized by a progressive decline in the function of many organs and tissues that, in some cases, can contribute to the development of cancer [14]. The hematopoietic system undergoes alterations with age, which affects the performance and number of HSCs and the composition of blood cells [15], increasing the likelihood of acquiring age-related blood illnesses such as anemia, a weakened immune response, and blood cancer. After a defined period, blood cells undergo differentiation and maturation and are eventually destroyed, preserving the equilibrium state. Hematological disorders are medical ailments characterized by an imbalance in homeostasis [10]. Hematopoietic tissue cancer (blood cancer) is a malignancy that originates in bone marrow [8] and is characterized by the excessive growth of abnormal blood cells [16]. These disorders are due to abnormalities in HSCs, the initiating cells in the hematopoietic system. Therefore, targeting only specific cells while minimizing damage to normal cells remains challenging [17,18]. Consequently, stem cell therapy is emerging as a promising alternative for treating hematological diseases, including those related to aging.

Stem cell therapy is highly regarded for its potential in treating not only blood-related diseases but also for regenerating damaged tissues and organs. Stem cells used in related research encompass various types, including adult stem cells such as HSCs and mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) created by reprogramming somatic cells back to a pluripotent state [19,20]. MSCs, being multipotent stromal cells, exhibit the capacity to differentiate into a variety of cell types, including bone, cartilage, and adipocytes [20,21,22,23]. Consequently, numerous research findings have suggested their therapeutic potential in diverse diseases such as cartilage regeneration [24,25] and neurological disease recovery [25,26,27,28]. ESCs present immense therapeutic promise, as they can differentiate into all cell types in the body [29,30]. However, research in this domain is constrained by ethical dilemmas surrounding the extraction of stem cells from embryos [19]. iPSCs are anticipated to circumvent these ethical issues while offering utility akin to ESCs. Nonetheless, challenges persist in the reprogramming process, and uncertainties exist regarding their stability [19]. Despite active research and reporting on the therapeutic potential of stem cell therapy, many facets of stem cell biology remain unexplored, including fundamental mechanisms governing stem cell behavior and their interactions with the host environment. Consequently, stem cell therapy has not yet attained widespread adoption as a standard treatment. This review focuses on HSCs and their microenvironment to enhance our understanding of stem cell therapy, especially hematopoietic stem cell therapy.

HSCs are a rare population of multipotent cells, responsible for replenishing all blood cell types throughout an individuals lifetime. They have the unique ability to self-renew and differentiate into several types of blood and immune cells. This process, which produces all types of blood cells, is called hematopoiesis (Figure 1) [9]. HSCs produce hematopoietic progenitor cells through differentiation, which differentiate further to produce blood and immune cells [1]. However, hematopoiesis is a highly regulated process and typically unidirectional; once HSCs differentiate into hematopoietic progenitor cells, they cannot regenerate into HSCs [1]. Additionally, HSCs are used in transplantation therapy after irradiation to treat patients with blood cancer [19]. Unlike solid cancers, which can be selectively targeted and treated, blood cancers present significant challenges for treatment with conventional chemotherapy and radiation. For this reason, HSC transplantation remains one of the most effective and promising approaches, with significant ongoing research focusing on its potential [10].

HSCs predominantly reside in a specialized microenvironment within the bone marrow, known as the endosteum [2,9]. In this niche, HSCs remain dormant under stable conditions. When blood cells decrease due to stressors, such as bleeding, illness, or radiation, HSCs activate and reorganize the hematopoietic system by proliferating and differentiating into new cell types [1]. The equilibrium between the quiescent state and the division of HSCs is crucial for maintaining normal hematopoiesis. If this equilibrium is not adequately regulated, HSCs may decrease in number or give rise to blood malignancies such as leukemia (Figure 1). Thus, the equilibrium between the dormant and active phases of HSCs is tightly controlled by both internal and external mechanisms.

Blood is an essential regenerating tissue that is susceptible to changes and deterioration with age [12,13,31]. Aging is accompanied by various clinically significant conditions that affect the hematopoietic system [14], including a decline in the adaptive immune system, an increased occurrence of specific autoimmune diseases, a higher prevalence of hematological malignancies, and an increased likelihood of age-related anemia [32]. An age-related decline in the functional capacity of HSCs has been widely recognized in studies conducted on mouse models [33]. When comparing young HSCs to old ones, the latter exhibit a preference for the myeloid lineage and have a reduced ability to regenerate when transplanted [33]. In addition, like many other tissues, the hematopoietic system is more likely to develop cancer with age, including a higher incidence of chronic and acute leukemia [14]. Given that myeloid leukemia is more common in older individuals and juvenile leukemia typically affects the lymphatic system, age-related alterations in HSCs may directly influence the development of disorders associated with blood cell formation [15]. Aged HSCs show increased expressions of genes implicated in the progression of myeloid leukemia, such as AML, PML, and ETO. Alternation of these gene expressions during normal hematopoiesis can result in impaired self-renewal capacity of HSC, heightened susceptibility to DNA damage, and aberrant differentiation potential. These alternations on HSCs are characteristic features of aged HSCs. Consequently, they are deemed suitable targets for investigating HSC aging and comprehending the molecular mechanisms underlying age-related hematopoietic dysfunction and leukemogenesis [32,34,35,36,37,38].

Multiple studies have documented the deterioration of HSCs in older mice, although the specific molecular processes responsible for this aging phenomenon remain unclear [14,15,31,32,33]. The aging of HSCs is limited by their diversity. The purity of HSCs isolated using flow cytometry has consistently been poor, indicating that the population becomes more heterogeneous as individuals age [15]. Ongoing research aims to identify specific subsets of HSCs that contribute to the aging phenotype [11]. This is achieved through the examination of age-dependent diverse pools of HSCs using single-cell bone marrow transplantation, flow cytometry, and single-cell transcriptome sequencing [15,32,39]. Specifically, HSC clones that undergo myeloid differentiation progressively occupy the HSC reservoir with age [39]. In this aspect, multiple research findings have been reported concerning the correlation between clonal hematopoiesis and aging [40]. Clonal hematopoiesis (CH) is a condition characterized by the expansion of specific HSC clones that acquire somatic mutations (e.g., DNMT3A, TET2, and ASXL) [41,42]. These mutations are thought to confer a selective advantage to HSCs, leading to the predominance of these clones in the blood system and allowing them to outcompete normal HSCs and expand clonally. While the specific signaling pathways involved in this process may vary depending on the gene and context, some common themes have emerged. For example, mutations in DNMT3A [43,44], TET2 [45,46,47], and ASXL1 [48] are known to affect epigenetic regulation, leading to alterations in gene expression patterns and cellular differentiation pathways [42,49]. Additionally, these mutations may impact other signaling pathways related to cell survival, proliferation, and self-renewal [48]. However, the exact signaling pathways or mechanisms through which these mutations lead to clonal expansion are still under investigation and continue to be an active area of research. This phenomenon becomes increasingly common with age and is associated with a higher risk of hematologic malignancies and cardiovascular diseases [41,50,51]. Research indicates that approximately 1020% of individuals over 70 years old exhibit clonal hematopoiesis, highlighting its prevalence in the elderly population.

CH not only alters the composition of the hematopoietic system but also impacts the bone marrow microenvironment, known as the niche, which is crucial for maintaining HSC function and homeostasis. Aging induces significant changes in the bone marrow niche, including a decline in the number and function of MSCs, osteoblasts, and endothelial cells [41,52]. These alterations, coupled with the production of elevated levels of inflammatory cytokines such as IL-6 and TNF- by mutant HSCs and the aging niche, create a pro-inflammatory and oxidative stress environment [47,53,54]. This environment promotes the expansion of CH, impairs normal HSC function, and decreases the secretion of essential factors for HSC maintenance, thus exacerbating the proliferation of clonal HSCs and diminishing the niches ability to support normal hematopoiesis. Although there have been numerous reports on the heterogeneity of HSCs associated with aging, our understanding of the effects of aging remains uncertain, and requires further investigation.

A recent study investigated the functional alterations that occur in aged HSCs within the mitochondrial metabolic milieu [12,13,14]. Specifically, the properties and roles of young and aged HSCs are influenced by the mitochondrial membrane potential within these cells [55]. Researchers reversed aging in old mice by manipulating the mitochondrial membrane potential of aged HSCs using the antioxidant Mito-Q [31]. Clinical utilization of Mito-Q is a possible preventative measure and treatment for age-related blood disorders.

HSCs typically reside in the bone marrow (BM), which is composed of various components, including bone, blood vessels, and other cells and substrates filling the spaces between them [2]. This BM microenvironment, known as a Niche, provides a structural framework and communication networks to HSCs [2,7].

This microenvironment can control the state of HSCs by direct or indirect interactions and safeguard them from sustaining their undifferentiated state [2,7,9]. It engages HSCs to control their growth and specialization through distinct signal transduction processes, resulting in regular hematopoiesis [7]. Recent advancements in single-cell analysis techniques have revolutionized our understanding of the BM niche, shedding light on its cellular composition, spatial organization, and dynamic interactions with HSCs. One of the key insights gleaned from single-cell analysis is the dynamic nature of the BM niche [56]. Studies have revealed the presence of specialized niches within the BM, each tailored to support specific stages of hematopoietic development [57,58]. Moreover, single-cell analysis has unveiled the plasticity of niche cells, demonstrating their ability to dynamically respond to extrinsic signals and adapt to changing physiological conditions [59,60]. Furthermore, single-cell analysis has provided insights into the spatial organization of the bone marrow niche, uncovering intricate spatial relationships between niche components and HSCs. Spatial transcriptomics techniques have revealed specialized niches localized within specific anatomical regions of the BM, highlighting the importance of spatial context in regulating hematopoietic function [58,61,62,63].

Depending on their spatial location, niches can be divided into an osteoblastic niche, which is the area near the endosteum, and a vascular niche, where blood vessels and surrounding matrix exist in the BM [58]. In addition, various immune cells derived from HSCs (including T/B lymphocytes, macrophages, natural killer cells, and dendritic cells) or the stromal cells contribute to configuring the BM microenvironment. These cells interact with HSCs, participating in the regulation of their state. Non-cellular substances can also serve as nutrients for HSCs, providing essential support for their growth and maintenance. These substances may include growth factors, cytokines (e.g., SCF, interleukins, CXCL12), and extracellular matrix components present in the BM microenvironment. By interacting with HSCs, these non-cellular factors play a crucial role in regulating hematopoiesis and maintaining stem cell homeostasis.

The vascular niche is composed of endothelial cells and perivascular stromal cells (such as pericytes and smooth muscle cells) that make up blood vessels [64,65,66]. They provide structural support and produce niche factors essential for HSC maintenance, proliferation, and differentiation. Additionally, the extracellular matrix surrounding these niche cells serves as a dynamic scaffold that facilitates cellular interactions and regulates the release and localization of signaling molecules [67,68].

Vasculogenesis can be categorized into two stages: the embryonic and adult stages [2,9]. During the embryonic stage, there is a significant level of contact between HSCs and endothelial cells [69]. Hematopoietic and endothelial cells are derived from hemangioblasts, multipotent progenitor cells, during the embryonic stage [70]. Endothelial cells expressing RUNX1 can produce HSCs in the aorta, gonad, mesonephros, and placenta [71]. Both endothelial and hematopoietic stem cells co-express CD31, CD34, CD133, FLK1, and TIE2 [72]. HSCs release angiopoietin-1 (ANG1), which stimulates the growth of new blood vessels during angiogenesis [73]. Additionally, endothelial cells provide a similar microenvironment for HSCs as well as neural stem cells. In the hippocampus, neural stem and endothelial cells that generate fibroblast growth factor (FGF), another angiogenesis-promoting substance, are close to each other [74].

However, the precise nature of the interaction between endothelial cells and bone marrow HSCs in the adult stage remains unclear. BM-derived endothelial progenitor cells participate in postnatal angiogenesis [75]. A conceptual framework for the vascular environments in bone marrow has been suggested, wherein the activation of MMP9 expressed in the osteoblast region results in the separation of the Kit ligand from the cell membrane of stromal cells in the BM. Subsequently, the soluble Kit ligand stimulates the initiation of the cell cycle and enhances the activity of HSCs [76]. Thus, HSC activity, proliferation, and differentiation occur in the vascular niche within the BM [69]. Vascular endothelial growth factor (VEGF) and ANG1 are angiogenic factors that play crucial roles in preserving HSCs [77]. VEGF controls the development of blood vessels and hematopoiesis and regulates hematopoietic stem cells through an internal autocrine loop [78]. HSCs remain inactive in osteoblastic niches, whereas both hematopoietic stem and progenitor cells undergo division in vascular habitats. Hematopoietic cell migration commences in stem cells located in the osteoblast niche where they then proliferate, differentiate, and ultimately mature [7]; cells migrate toward the vascular niche via this process.

To maintain hematopoietic homeostasis, the process of homing, wherein hematopoietic stem and progenitor cells (HSPCs) circulating through the blood return to the BM niche, is also essential [79,80,81]. In this process, HSPCs directly interact with the endothelium via cellcell adhesive interaction. Sinusoidal endothelial cells express adhesion molecules, including P-selectin (CD62P), E-selectin (CD62E), and vascular cell adhesion molecule-1 (VCAM-1 or CD106). Several receptors for these molecules are expressed in HSPCs, including P-selectin glycoprotein ligand-1 (CD162) and CD44, along with other less well-defined E-selectin receptors. Additionally, receptors for VCAM-1, such as integrins 41, 47, and 91, are also expressed.

The other components such as pericytes and smooth muscle cells also play an important role in regulating the behavior of HSCs [82,83]. Leptin-receptor-positive (LepR+) cells and CXCL12-abundant reticular (CAR) [82] cells are well-established cells that secrete growth factors essential for the maintenance of HSCs. They are located along the blood vessels of mainly the sinusoids, playing a crucial role in regulating vascular stability and function. CXCL12 and SCF from them are key factors for HSC proliferation [84]. This was confirmed through experiments deleting CXCL12 secreted by LepR+ cells and CAR cells. Deletion of CXCL12 in these cells results in the removal of all quiescent and serially transplantable HSCs from adult bone marrow. This occurs because signaling with CXCR4, receptors on HSCs, is reduced, demonstrating that CXCL12 from LepR+ cells and CAR cells play a central role in the signaling that maintains the pool of HSCs [85].

Conversely, Nestin-positive (Nes+) cells found exclusively around arterioles provide support, contrasting with perivascular cells around sinusoids [86]. Nes+ cells also secrete soluble factors like CXCL12 and SCF, which tend to drive quiescent HSCs into early hematopoietic stages and promote HSC activation, leading to differentiation [87].

Osteoblasts, layering the endosteal bone surface and providing an osteoblastic niche to HSCs, regulate hematopoiesis [7,88]. They provide a supportive environment for HSCs, regulating their self-renewal, differentiation, and quiescence. Osteoblasts produce niche factors and adhesion molecules that interact with HSCs, influencing the maintenance of HSCs in a dormant state and their activation in response to hematopoietic demand [89]. Osteoblasts have a critical role in the regulation of the physical location and proliferation of HSCs by expressing osteopontin (OPN). OPN specifically binds to beta1 integrin expressed on HSCs [90]. The other key factor expressed in osteoblasts is angiopoietin-1 (ANG1). Interaction of Tie2 and ANG1, the receptor of ANG1 expressed on HSCs, vital for maintaining HSCs in the quiescent state, preserves their long-term self-renewal potential and prevents exhaustion [39]. This signaling helps to retain HSCs in the bone marrow niche and prevents their premature differentiation or migration [91,92,93].

Through long-term in vivo labeling with 5-bromodeoxyuridine (BrdU), most HSCs divide [94]. However, some HSCs were found to be dormant, retained their labels, and remained dormant for several months. Therefore, bone marrow cells can be classified into resting and dividing HSCs. Resting HSCs are located close to osteoblasts [7]. Using Bmpr1a KO mice, Zhang et al. showed that N-cadherin+ spindle-shaped osteoblasts resemble HSCs with a slow cell cycle [94]. Their study revealed that osteoblast cells expressing N-cadherin in the bone marrow act as nests for HSCs, and that an increase in the number of N-cadherin+ cells is associated with an increase in HSCs. Additionally, Visnjic et al. showed that hematopoiesis is suppressed in osteoblast-deficient mice [95]. Thus, it was confirmed that defects in HSC osteoblasts inhibit hematopoiesis. The Notch signaling pathway, characterized by membrane-bound ligands, regulates cell fate determination across various systems, including the self-renewal of HSCs [96,97,98,99,100]. In the study by Calvi et al. [101], they found that PPR-stimulated osteoblasts express a high level of Notch ligand jagged 1 using the transgenic mouse of PTH/PTHrP receptors (PPRs). In response, the activation of the Notch1 intracellular domain (NICD) in Lin-Sca-1+c-Kit+ HSCs increased. Additionally, when HSCs were long-term co-cultured with a Notch cleavage inhibitor, the support for HSCs observed in transgenic stroma decreased to a similar level to their isotype control. Another study, using RAG-1-deficient mice essential for V(D)J recombination and lymphocyte development, showed that Notch1 activation leads to inhibition of HSC differentiation [98]. This confirms that interaction between osteoblasts and HSCs via the Notch pathway plays a crucial role in regulating HSC behavior within the bone marrow niche.

In addition to spatially distinct osteoblastic and vascular niches, stromal cells and immune cells play roles within the microenvironments of HSCs in bone marrow [62,63,102,103,104]. They can either directly interact with HSCs or regulate them indirectly by secreting soluble factors such as growth factors, cytokines chemokines, and other signaling molecules.

Macrophages in the bone marrow play a crucial role in the formation of HSCs [63,105,106,107,108,109,110,111]. CD169+ macrophages, associated with the clearance of blood-borne pathogens and regulation of immune responses, play a crucial role in maintaining the quiescent state of HSCs [105]. They interact with Nestin-positive (Nes+) cells to promote the transcription of CXCL12 and other factors (such as HSC maintenance and retention factors ANG, KITl, VCAM1) essential for HSC maintenance. Depletion of macrophages leads to the loss of these factors and subsequent egress of HSCs from the bone marrow [105,106]. A subset of macrophages called Osteomacs reside adjacent to osteoblasts and megakaryocytes along the bone lining, distinct from osteoclasts. These osteomas have been identified to play crucial regulatory roles in modulating osteoblast function. Their interaction with osteoblasts is essential for the low-level activation of nuclear factor B (NF-B) in osteoblasts, enabling them to maintain HSCs through appropriate chemokine signaling. Furthermore, the presence of megakaryocytes supports the function of osteomacs, and their synergistic interactions with osteoblasts contribute to the regulation of HSC repopulating potential, as evidenced by transplantation assays [107,108,109,110,111]. Although significant progress has been made in understanding the role of macrophages in HSC behavior [106], the specific signaling pathways and the diverse functions associated with macrophage heterogeneity are not yet fully understood. Therefore, ongoing additional studies are needed to fully elucidate the multifaceted roles of macrophages in hematopoiesis and their potential therapeutic applications.

Megakaryocytes also govern the viability of HSCs [112,113,114]. Megakaryocyte removal from the bone marrow leads to an increase in the number of HSCs. HSCs exhibited a compensatory increase in mice experiencing bleeding. However, this compensatory increase is restricted when blood cells are introduced into the bloodstream [113]. Megakaryocytes have been suggested to restrict the proliferation of HSCs in two ways. The first mechanism involves the production of CXCL4 by megakaryocytes, which inhibits HSC proliferation [112]. The second mechanism involves the action of TGF, which controls the inactive state of the HSCs [113]. Additionally, megakaryocytes influence myeloid-biased HSC activity and act as a physical barrier to HSC migration. Thrombopoietin (TPO) production by megakaryocytes further regulates hematopoietic activity. Depletion of megakaryocytes in mice resulted in decreased megakaryopoiesis, alongside lower numbers of HSCs and reduced HSC quiescence [115,116,117,118].

Chemokines, also known as chemo-attractant proteins, play crucial roles in regulating the movement of HSCs and facilitating their contact with stromal cells [119]. CXCL12, also known as SDF1, is a chemokine involved in cell homing. Deletion of SDF1 or its receptor CXCR4 leads to normal fetal heart hematopoiesis; however, there is a failure of bone marrow engraftment by hematopoietic cells [120,121]. Upregulation of CXCR4 in human hematopoietic progenitor cells results in enhanced engraftment in nude mice, whereas the use of CXCR4-neutralizing antibodies demonstrates an inhibitory effect on engraftment [122]. However, CXCR4 is not typically found in HSCs that are not actively dividing. This identifies the factors for successful HSC attachment and the molecules responsible for binding to osteoblasts. Osteoblasts express the adhesion molecules ALCAM and osteopontin, which may play a role in the interaction between HSCs and osteoblasts [123]. Furthermore, it is assumed that external factors such as BMPs, NOTCH ligands, and angiopoietins in bone marrow niches play a role in the interaction between HSCs and osteoblasts [94,101]. In some research, depletion of CXCL12 in osteoblasts resulted in the selective loss of B-lymphoid progenitors. Studies have shown that acute inflammation can inhibit osteoblastic bone formation, leading to T and B lymphopenia due to decreased production of interleukin-7 (IL-7). This suggests that osteoblasts may regulate common lymphoid progenitors by supplying IL-7 [124,125,126].

Myeloid lineage cells, including granulocytes and dendritic cells, also impact the HSC niche [127]. Granulocytes produce factors like G-CSF (granulocyte colony-stimulating factor), which promotes HSC mobilization from the bone marrow into the bloodstream. Dendritic cells contribute to HSC maintenance by modulating the expression of adhesion molecules and cytokines within the niche.

Due to the characteristics of HSCs, their self-renewal, multiple differentiation, and interactions with niche components, they can be used for the therapy of some blood-related diseases. Transplanting HSCs can restore patients HSC pools and also regenerate immune cell populations, which means that abnormal hematopoiesis has been replaced with normal hematopoiesis [128]. Hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplantation, is utilized as a therapeutic approach for various blood-related diseases. HSCT offers a powerful therapeutic option by essentially resetting the hematopoietic and immune systems, allowing for the restoration of normal function and providing a potential cure for many serious conditions. It can be applied to patients as a therapeutic approach for various blood-related diseases, including malignant blood disorders such as lymphoma, multiple myeloma, and leukemia, as well as aplastic anemia and immunodeficiency disorders. It is especially considered in relapsed or refractory cases that do not respond to conventional chemotherapy or radiotherapy and in aggressive forms (e.g., diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma) [22,129,130,131].

Unlike solid organ transplantation, where the main goal is organ replacement, allogeneic hematopoietic cell transplantation for hematologic malignancies focuses on regulating the immune response against the underlying cancerous condition [128,132]. In leukemia, normal hematopoietic microenvironments are transformed into leukemic microenvironments by leukemic stem cells (LSCs). LSCs exhibit a high propensity for proliferation rather than differentiation into subset populations and possess strong resistance to drugs, resulting in poor prognosis and leukemia relapse [132,133,134,135,136]. For bone marrow transplantation, the most important thing is donor selection [137]. It is crucial to match the donors human leukocyte antigen (HLA) with the recipients as closely as possible to minimize the risk of graft rejection and graft-versus-host disease (GVHD). GVHD is a significant complication following HSCT, where donor immune cells attack the recipients tissues, leading to organ damage [138,139]. Immune checkpoint molecules such as TIGIT, PD-1, CTLA-4, and TIM-3 play pivotal roles in regulating immune responses in GVHD [140,141]. TIGIT and PD-1 inhibit T cell activation and effector functions [140,142,143,144,145,146], while CTLA-4 competes with CD28 for ligand binding, thereby inhibiting T cell activation [141,147]. TIM-3 regulates T cell exhaustion and tolerance [148,149]. Dysregulation of these markers can disrupt immune homeostasis, exacerbating GVHD pathology. Understanding the functions of immune checkpoint molecules is crucial for developing targeted therapies to mitigate GVHD severity post-HSCT. In a German study, after transplantation, the graft versus leukemia (GvL) effect in acute myeloid leukemia (AML) was found to significantly improve the 7-year relapse-free survival of patients with AML in first complete remission compared to conventional chemotherapy alone. This highlights its efficacy in disease control. However, transplantation at an advanced disease stage yields lower survival rates, emphasizing the importance of early consideration and referral for transplantation in eligible patients [150,151,152].

For successful transplantation, the recipients (patients) blood and immune system must initially be depleted by combinations of chemotherapy and radiotherapy [153]. Drugs used in conditioning therapy before bone marrow transplantation include cyclophosphamide, busulfan, melphalan, and fludarabine. These drugs induce apoptosis by interfering with DNA replication, transcription, and synthesis, thereby destroying the patients existing cells and suppressing the immune system. This helps prevent transplant rejection by adequately suppressing the immune system [154,155,156,157]. If this pre-HCT conditioning is performed well, donor HSCs can home to and engraft the recipients bone marrow, thereby reconstituting all the blood cell lineages. Immune recovery after HSCT occurs in phases, with innate immune cells and platelets generally recovering within weeks after HSCT; fully complete reconstitution of adaptive immunity may extend over months to even years (Figure 3) [158,159,160,161].

Dynamics of immune reconstitution and associated risks in recipients bone marrow following hematopoietic stem cell transplantation. In the first few weeks after transplantation, innate immune cells recover swiftly. Common infections during this phase include bacterial and Candida infections due to the early deficiency in adaptive immune cells. Meanwhile, adaptive immune function, including T cells and B cells, exhibits prolonged deficiencies and gradually recovers, taking over 2 years to fully restore. Viral infections and those caused by non-Candidal molds become more common during this phase. Various clinical factors, including conditioning regimens, donor sources, and post-transplant events such as graft-versus-host disease (GVHD) and immunosuppression, exert influence over the immune reconstitution process, thereby modulating the associated infectious risks.

During this process, various cells within the bone marrow serve as niche components for donor HSCs. The BM niche provides the microenvironment necessary for hematopoietic stem cell (HSC) maintenance, differentiation, and proliferation. Endothelial cells play a significant role in the regulation of various processes, including the quiescence, proliferation, and mobilization of HSCs. It is anticipated that ECs will aid in the hematopoietic recovery of donor HSCs following transplantation. Although ECs are often damaged during conditioning for HCT, when transplanted alongside HSCs, they have been shown to confer beneficial effects in terms of HSC engraftment, reconstitution, and survival post-irradiation [162,163,164]. MSCs, as a rare component of the bone marrow niche, play a crucial role in regulating HSC homeostasis through the production of key soluble factors. Different subsets of MSCs have distinct impacts on HSC behavior, supporting either quiescent or proliferative states. Despite surviving conditioning regimens, MSCs may accumulate damage, potentially affecting their functionality. In clinical contexts, MSCs have shown promise in enhancing HSC engraftment and treating complications like steroid-resistant aGvHD, although further research is needed to elucidate their precise mechanisms of action [165,166,167].

Hematopoietic stem cells (HSCs) possess the remarkable ability to generate all lower cells of the hematopoietic hierarchy and regulate the entire process of hematopoiesis through self-renewal and proliferation. The uninterrupted generation of new blood cells is indispensable for the survival of organisms, underscoring the critical importance of maintaining the normal function of HSCs throughout life. Normal hematopoiesis involves maintaining a good balance between activated HSCs that produce blood and quiescent HSCs that do not function. However, when HSCs are damaged due to various factors, such as aging, their function is compromised, leading to aberrant hematopoiesis and potentially giving rise to hematological diseases, including aplastic anemia, myelodysplastic syndromes, and leukemia.

Aging affects the overall functioning of an organism, and blood production is also strongly affected. Various research results have revealed that aging affects the function of HSCs, causing their parts to change abnormally. Functional and genomic analysis has been conducted through mouse experiments, and the phenotype in elderly people is similar. Aging eventually causes diseases such as immune disorders, lymphoma, and leukemia, and the prognosis is worse for elderly patients whose hematopoiesis and immune systems have already collapsed.

The niche of HSCs interacts with cells in various aspects to regulate their functions. Osteoblast cells in the bone-adjacent area of the bone marrow lumen play a crucial role in regulating the state of HSCs through various mechanisms. Osteoblasts express Ang1 and OPN, which bind to specific receptors expressed on HSCs, causing them to remain stationary in a specific area. This interaction helps maintain the quiescent state of HSCs and regulates their retention within the bone marrow niche.

Vascular tissue refers to vascular components including vascular endothelial cells, pericytes, and SMCs, as well as stromal cells, which are supporting cells around them. Endothelial cells (ECs) and pericytes are classified according to the location of blood vessels (sinusoids or arterioles), and they both regulate HSCs by secreting various chemokines, including CXCL12 and SCF. These soluble factors perform different functions depending on their site of secretion, either promoting the quiescence or activation of HSCs.

HSC transplantation is gaining attention as a treatment for diseases stemming from HSC damage, particularly leukemia. Just as HSCs interact with niche components to sustain ongoing hematopoiesis, hematopoiesis can be restored by transplanting HSCs from a healthy donor into patients with HSC or niche defects. However, due to the limited understanding of the niche in the context of bone marrow transplantation, ongoing research is crucial to address issues like GVHD.

Writingoriginal draft preparation, M.K.; conceptualization, B.S.K., S.Y., S.-O.O. and D.L.; funding acquisition, D.L. All authors have read and agreed to the published version of the manuscript.

The authors declare no conflicts of interest.

This research was supported by grants from the Korean Cell-Based Artificial Blood Project funded by the Korean government (The Ministry of Science and ICT; the Ministry of Trade, Industry, and Energy; the Ministry of Health & Welfare; the Ministry of Food and Drug Safety) [grant no. HX23C1692], and grants from the Basic Science Research Program through the National Research Foundation (NRF) of Korea, funded by the Ministry of Education and the Ministry of Health & Welfare [grant nos. 2022R1A5A2027161, RS-2023-00223764, and RS-2024-00333287].

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Hematopoietic Stem Cells and Their Niche in Bone Marrow

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Todays ecosystem is based around living volunteers, Ossiums CEO and cofounder, Kevin Caldwell, says. While the US organ donor system has existed for decades, bone marrow has never been regularly collected from those deceased donors in the same way that hearts, lungs, kidneys, and livers have. Nobody had come up with an efficient way of obtaining the cells from deceased donors or cryopreserving them at scale so they can be stored until needed.

Ossium CEO and cofounder Kevin Caldwell.

Unlike a solid organ, you cant just transplant bone marrow into the nearest person who is roughly the right size who needs it, Caldwell says. You really have to have a close genetic match between the donor and the recipient.

The new method of stem cell harvesting, via apheresis, doesnt work well in deceased people because it relies on blood pressure. Based on previous research conducted at the University of Pittsburgh and Johns Hopkins University, Ossium developed a way to extract bone marrow from the spinal column, a part of the body that typically went unused. The company has partnered with US organ procurement organizations to recover spinal columns from cadavers and ship them to the companys facility in Indianapolis. There, bone marrow is extracted and cryopreserved in liquid nitrogen vapor at about 190 degrees Celsius.

Caldwell says Ossium has processed thousands of donors since the company was founded in 2016. (The exact number of donors in the bank is proprietary, he says.) Ossiums frozen bone marrow has now been given to three people in total, including the Michigan woman, with a fourth transplant scheduled soon.

Robert Negrin, a professor of medicine at Stanford University and vice president of the American Society of Hematology, calls the transplants an important milestone, but whether the technique will be useful for cancer patients remains to be seen. We have other options that work pretty well, he says, referring to partially matched donor transplants and cord blood transplants. But there are always situations that could fall through the cracks.

Negrin sees potential for deceased donor bone marrow transplants to help organ transplant patients, who currently must take immunosuppressive drugs for the rest of their lives to avoid their immune system attacking the new organ. But because immune cells originate in the bone marrow, if they could receive a marrow transplant from the same donor, Negrin says patients couldin theorygo off immunosuppressive drugs.

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Bone Marrow Donors Can Be Hard to Find. One Company Is Turning to Cadavers  WIRED

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Bone marrow transplant patient care

You will be cared for by a team of experts in bone marrow transplant.

Mayo Clinic's bone marrow (stem cell) transplant team is recognized internationally for its expertise in comprehensive specialty treatment for people with blood and bone marrow diseases. Mayo Clinic is one of the largest providers of bone marrow transplants in the United States. It has performed more than 10,000 stem cell transplants at its campuses in Arizona, Florida and Minnesota.

At Mayo Clinic, bone marrow transplant experts help adults and children with leukemia and other blood, plasma and bone marrow diseases. Your doctors will talk with you about all treatment options appropriate for you, including experimental treatments, and deliver care tailored to your needs.

Mayo Clinic bone marrow transplant experts are involved in patient care and research in the Mayo Clinic Comprehensive Cancer Center, designated by the National Cancer Institute as a comprehensive cancer center. The Mayo Clinic Comprehensive Cancer Center ranks in the top tier of cancer centers in the United States for Cancer research, treatment and education. Mayo Clinic Comprehensive Cancer Center is also a member of the National Comprehensive Cancer Network.

Your bone marrow transplant team collaborates to ensure you get exactly the care you need.

Mayo Clinic's experts focus on your needs, bringing to your situation the strength of their:

Experience. Specialists in bone marrow transplant and hematology at Mayo Clinic have extensive experience helping people with all types of diseases, including very rare ones. For example, they are leaders in the use of blood stem cell transplants to treat amyloidosis.

Each year, more than 30,000 people with blood diseases are treated at Mayo Clinic, and more than 700 of them undergo bone marrow transplants. This experience means your doctors are prepared with the knowledge and resources to provide exactly the care you need.

Innovative research. Mayo Clinic researchers make bone marrow transplants safer and improve the lives of people who need them. Their innovative treatments harness the body's immune system, make use of new stem cell technologies and prevent complications such as graft versus host disease.

Mayo Clinic bone marrow transplant physicians and hematologists work with other hospitals in the United States and internationally to conduct clinical trials. The close connection between clinical care and research at Mayo Clinic makes it possible for eligible patients to enroll in clinical trials, where they may receive new treatments.

Mayo Clinic bone marrow transplant experts and hematologists are also involved in patient care and research in the Mayo Clinic Comprehensive Cancer Center. This center ranks in the top tier of cancer centers in the United States.

At Mayo Clinic's campus in Minnesota, children and adolescents with blood disorders receive care through the Children's Center. Children needing hospitalization receive care at Mayo Eugenio Litta Children's Hospital.

At Mayo Clinic's campus in Arizona, doctors trained in blood diseases and cancer (hematologists and oncologists) partner with Phoenix Children's Hospital to treat children who may need bone marrow transplants. Together the two hospitals oversee a single bone marrow transplant program for children.

At Mayo Clinic's campus in Florida, hematologists and oncologists partner with Nemours Children's Specialty Care and Wolfson Children's Hospital to treat children who may need bone marrow transplants.

Mayo Clinic's Bone Marrow Transplant Program provides consultations, evaluations and treatment for patients who would potentially benefit from a bone marrow transplant.

Mayo Clinic bone marrow transplant specialists work with a multidisciplinary team to determine the most appropriate treatment for you. They have expertise in many areas of bone marrow transplant, including those listed below. Not all services are available at each of Mayo Clinic's three campuses in Arizona, Florida and Minnesota. Please confirm when you call to request an appointment.

Mayo Clinic in Rochester, Minnesota, Mayo Clinic in Jacksonville, Florida, and Mayo Clinic in Phoenix/Scottsdale, Arizona, are ranked among the Best Hospitals for cancer by U.S. News & World Report.

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Bone Marrow Transplant Program - Overview - Mayo Clinic

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Skull bone marrow expands throughout life and remains healthy during aging, researchers discover  Medical Xpress

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Skull bone marrow expands throughout life and remains healthy during aging, researchers discover - Medical Xpress

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More stem cells for sickle cell gene therapy readied with motixafortide  Sickle Cell Disease News

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More stem cells for sickle cell gene therapy readied with motixafortide - Sickle Cell Disease News

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Adult skull bone marrow is an expanding and resilient haematopoietic reservoir  Nature.com

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Stem cells grown in space show super powers but theres a catch  Study Finds

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Evaluation of standard fludarabine dosing and corresponding exposures in infants and young children undergoing hematopoietic cell transplantation  Nature.com

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When the decision is made to have a stem cell or bone marrow transplant, there are several steps in theprocess. The steps are much the same, no matter what type of transplant youre going to have.

You will first be evaluated to find out if you are eligible for a transplant. A transplant is very hard on your body. For many people, transplants can mean a cure, but for some people, problems can lead to severe complications or even death. Youll want to weigh the benefits and risks before you start.

Transplants can also be hard emotionally. They often require being in the hospital, being isolated, and theres a high risk of side effects. Many of the effects are short-term, but some problems can go on for years. This can mean changes in the way you live your life. For some people its just for a while, but for others, the changes may be lifelong. Some of the side effects are really unpleasant and can be serious. Your cancer care team will do everything they can to make you comfortable, but some of the side effects may not be completely controlled or relieved.

Before you have a transplant, you need to discuss the transplant process and all its effects with your doctors. It also helps to talk with others who have already had transplants.

Its also very hard going through weeks and months of not knowing how your transplant will turn out. This takes a lot of time and emotional energy from the patient, caregivers, and loved ones. Its very important to have the support of those close to you. For example, youll need a responsible adult who will be with you to give you medicines, help watch for problems, and stay in touch with your transplant team after you go home. Your transplant team will help you and your caregiver learn what you need to know. The team can also help you and your loved ones work through the ups and downs as you prepare for and go through the transplant.

Many different medical tests will be done, and questions will be asked to try to find out how well you can handle the transplant process. These might include:

You will also talk about your health insurance coverage and related costs that you might have to pay.

You may have a central venous catheter (CVC) put into a large vein in your chest. This is most often done as outpatient surgery, and usually only local anesthesia is needed (the place where the catheter goes in is made numb). Nurses will use the catheter to draw blood and give you medicines.

If youre getting an autologous transplant, a special catheter can be placed that can also be used when your stem cells are being removed or harvested.

The CVC will stay in during your treatment and for some time afterward, usually until your transplanted stem cells have engrafted and your blood counts are on a steady climb to normal.

Younger people, people who are in the early stages of disease, or those who have not already had a lot of treatment, often do better with transplants. Some transplant centers set age limits. Some people also may not be eligible for transplant if they have other major health problems, such as serious heart, lung, liver, or kidney disease. A mini-transplant, described under Allogeneic stem cell transplant in Types of Stem Cell Transplants for Cancer Treatment may be an option for some of these people.

The hospitals transplant team will decide if you need to be in the hospital to have your transplant, if it will be done in an outpatient center, or if you will be in the hospital just for parts of it. If you have to be in the hospital, you will probably go in the day before pre-transplant chemo or radiation treatment begins (see the next section), the transplant team makes sure you and your family understand the process and want to go forward with it.

If you will be having all or part of your transplant as an outpatient, youll need to be very near the transplant center during the early stages. Youll need a family member or loved one to be a caregiver who can stay with you all the time. You and the caregiver will also need reliable transportation to and from the clinic. The transplant team will be watching you closely for complications, so expect to be at the clinic every day for a few weeks. You may still need to be in the hospital if your situation changes or if you start having complications.

To reduce the chance of infection during treatment, patients who are in the hospital are put in private rooms that have special air filters. The room may also have a protective barrier to separate it from other rooms and hallways. Some have an air pressure system that makes sure no unclean outside air gets into the room. If youre going to be treated as an outpatient, you will get instructions on avoiding infection. Usually, people who have transplants are in a separate, special part of the hospital to keep as many germs away as possible.

The transplant experience can be overwhelming. Your transplant team will be there to help you prepare for the process physically and emotionally and to discuss your needs. Every effort will be made to answer questions so you and your family fully understand what will be happening to you as you go through transplant.

Its important for you and your family to know what to expect, because once conditioning treatment begins (see the next section), theres no going back there can be serious problems if treatment is stopped at any time during transplant.

Having a transplant takes a serious commitment from you and your caregiver and family, so it is important to know exactly what to expect.

Conditioning, also known as pre-transplant treatment,bone marrow preparation, or myeloablation, is usually treatment with high-dose chemo and/or radiation therapy. Its the first step in the transplant process and typically takes a week or two. Its done for one or more of these reasons:

The conditioning treatment is different for every transplant. Your treatment will be planned based on the type of cancer you have, the type of transplant, and any chemo or radiation therapy youve had in the past.

If chemo is part of your treatment plan, it will be given in your central venous catheter and/or as pills. If radiation therapy is planned, its given to the entire body (called total body irradiation or TBI). TBI may be given in a single treatment session or in divided doses over a few days.

This phase of the transplant can be very uncomfortable because very high treatment doses are used. Chemo and radiation side effects can make you sick, and it may take you months to fully recover. A very common problem is mouth sores that will need to be treated with strong pain medicines. You may also have nausea, vomiting, be unable to eat, lose your hair, and have lung or breathing problems.

Conditioning can also cause premature menopause in women and often makes people sterile (unable to have children). (See Stem Cell Transplant Side Effects.)

After the conditioning treatment, youll be given a couple of days to rest before getting the stem cells. They will be given through your central venous catheter, much like a blood transfusion. If the stem cells were frozen, you might get some drugs before the stem cells are given. These drugs are used to help reduce your risk of reacting to the preservatives that are used when freezing the cells.

If the stem cells were frozen, they are thawed in warm water then given right away. There may be more than 1 bag of stem cells. For allogeneic or syngeneic transplants, the donor cells may be harvested (removed) in an operating room, and then processed in the lab right away. Once they are ready, the cells are brought in and given to you theyre not frozen. The length of time it takes to get all the stem cells depends on how much fluid the stem cells are in.

You will be awake for this process, and it doesnt hurt. This is a big step and often has great meaning for patientsand their families. Many people consider this their rebirth or chance at a second life. They may celebrate this day as they would their actual birthday.

Side effects from the infusion are rare and usually mild. The preserving agent used when freezing the stem cells causes many of the side effects. For instance, you might have a strong taste of garlic or creamed corn in your mouth. Sucking on candy or sipping flavored drinks during and after the infusion can help with the taste. Your body will also smell like this. The smell may bother those around you, but you might not even notice it. The smell, along with the taste, may last for a few days, but slowly fades away. Often having cut up oranges in the room will offset the odor. Patients who have transplants from cells that were not frozen do not have this problem because the cells are not mixed with the preserving agent.

Other side effects you might have during and right after the stem cell infusion include:

Again, side effects are rare and usually mild. If they do happen, they are treated as needed. The stem cell infusion must always be completed.

The recovery stage begins after the stem cell infusion. During this time, you and your family wait for the cells to engraft, or take, after which they start to multiply and make new blood cells. The time it takes to start seeing a steady return to normal blood counts varies depending on the patient and the transplant type, but its usually about 2 to 6 weeks. Youll be in the hospital or visit the transplant center daily for a number of weeks.

During the first couple of weeks youll have low numbers of red and white blood cells and platelets. Right after transplant, when your counts are the lowest, you may be given antibiotics to help keep you from getting infections. You may get a combination of anti-bacterial, anti-fungal, and anti-viral drugs. These are usually given until your white blood cell count reaches a certain level. Still, you can have problems, such as infection from too few white blood cells (neutropenia), or bleeding from too few platelets (thrombocytopenia). Many patients have high fevers and need IV antibiotics to treat serious infections. Transfusions of red blood cells and platelets are often needed until the bone marrow starts working and new blood cells are being made by the infused stem cells.

Except for graft-versus-host disease, which only happens with allogeneic transplants, the side effects from autologous, allogeneic, and syngeneic stem cell transplants are much the same. Problems may include stomach, heart, lung, liver, or kidney problems. (Stem Cell Transplant Side Effects goes into the details.) You might also go through feelings of distress, anxiety, depression, joy, or anger. Adjusting emotionally after the stem cells can be hard because of the length of time you feel ill and isolated from others.

You might feel as if you are on an emotional roller coaster during this time. Support and encouragement from family, friends, and the transplant team are very important to get you through the challenges after transplant.

The discharge process actually begins weeks before your transplant. It starts with the transplant team teaching you and your primary (main) caregiver about:

For the most part, transplant centers dont send patients home until they meet the following criteria:

(Why Are Stem Cell Transplants Used as Cancer Treatment? has more information about neutrophils, platelets, and hematocrit).

If you do not meet all of these requirements, but still dont need the intensive care of the transplant unit, you might be moved to another oncology unit. When you do go home, you might need to stay near the transplant center for some time, depending on your condition.

The process of stem cell transplant doesnt end when you go home. Youll feel tired, and some people have physical or mental health problems in the rehabilitation period. You might still be taking a lot of medicines. These ongoing needs must now be managed at home, so caregiver and friend/family support is very important.

Transplant patients are followed closely during rehab. You might need daily or weekly exams along with things like blood tests, and maybe other tests, too. During early rehab, you also might need blood and platelet transfusions, antibiotics, or other treatments. At first youll need to see your transplant team often, maybe even every day, but youll progress to less frequent visits if things are going well. It can take 6 to 12 months, or even longer, for blood counts to get close to normal and your immune system to work well. During this time, your team will still be closely watching you.

Some problems might show up as much as a year or more after the stem cells were infused. They can include:

Other problems can also come up, such as:

Your transplant team is still there to help you, even though the transplant happened months ago. Its important that you tell them about any problems you are having they can help you get the support you need to manage the changes that you are going through. They can also help you know if problems are serious, or a normal part of recovery. The National Bone Marrow Transplant Link helps patients, caregivers, and families by providing information and support services before, during, and after transplant. They can be reached at 1-800-LINK-BMT (1-800-546-5268) or online at http://www.nbmtlink.org.

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Getting a Stem Cell or Bone Marrow Transplant

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1.5 Lakh Indians Register To Save Lives: Join the Mission To Fight Blood Cancer  The Better India

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Acquisition of durable insulin-producing cells from human adipose tissue-derived mesenchymal stem cells as a foundation for cell- based therapy of diabetes mellitus  Nature.com

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A stem cell transplant (also known as a bone marrow transplant) is a procedure in which defective or cancerous bone marrow is replaced with new, healthy bone marrow cells. A stem cell transplant may be used to treat leukemia and lymphoma, cancers that affect the blood and lymphatic system. Additionally, transplants are used to treat hereditary blood disorders, such as sickle cell anemia, and autoimmune diseases, such as multiple sclerosis. They also can help patients recover from or better tolerate cancer treatment.

Stem cells are specialized cells that can mature into different kinds of cells, depending on what your body needs. They are located in various places throughout your body, including your bone marrow. Bone marrow contains hematopoietic stem cells that constantly divide to produce all the different kinds of blood cells. Young hematopoietic stem cells can mature into any of the following cell types:

Any disease or condition that impacts the ability of your bone marrow to produce new blood cells can have serious health consequences. Bone marrow transplantation may be an effective treatment for such conditions.

In general, the first step to a successful stem cell transplant is harvesting healthy bone marrow, either from the patient or from a donor. This involves putting the patient or donor under general anesthesia and using a large needle to remove bone marrow from their pelvis. The bone marrow can then be frozen and stored. When it is ready for use, it is thawed and injected into a patient, much like a blood transfusion. The healthy stem cells will travel to bone marrow sites and start making blood cells.

There are two types of stem cell transplantation:

In an autologous stem cell or bone marrow transplant, healthy cells are harvested from the bone marrow of a patient. The harvested bone marrow is frozen and stored until it is ready for use. In the meantime, the patient undergoes a 'conditioning regimen' to prepare their body for the transplant. In this regimen, they may receive high dose chemotherapy r radiation therapy. These treatments destroy cancer cells, but they also kill bone marrow cells. This is where the transplant comes in. The patient is injected with their own stored blood stem cells. These cells 'take' to the body and restore its ability to produce blood cells.

Autologous transplantation is most often used to treat diseases like lymphoma and multiple myeloma. Because autologous transplants use the cells of a patient, they have little to no risk of rejection or graft-versus-host disease (GVHD).This makes it safer than allogeneic transplants.

An allogeneic bone marrow or stem cell transplant uses donor stem cells to treat blood cancers that affect the bone marrow, like leukemia. The cell transplants come from a donor whose tissue most closely matches that patient. The donor cells are injected after the patient has undergone chemotherapy. But beyond restoring the blood-producing ability of the body, allogeneic stem cell transplantation can help fight cancer directly. The donated cells generate a new immune response, meaning they find and kill cancer cells, sometimes better than the original immune cells of the patient. This is called the graft-versus-cancer effect, and it can help fight cancer. Unfortunately, allogeneic stem cells come with an increased risk of rejection or GVHD.

For allogeneic transplants to work, a patient needs to be matched with a donor whose human leukocyte antigen (HLA) proteins closely match theirs. HLA proteins dot your cells' surface and help your body distinguish normal cells from foreign cells. If the HLA proteins of a donor are a poor match to a patient, there is an increased risk of GVHD.

HLA typing is the process by which stem cell transplant patients are matched with eligible donors. In HLA typing, a blood sample from a patient is compared with samples from family members or a donor registry. The best match is usually a first-degree relative (children, siblings, or parents). However, about 75% of patients do not have suitable donors in their family and require cells from a matched unrelated donor (MUD). Stem cell donors are located through registries such as the National Marrow Donor Program. It can sometimes take several weeks or longer to find a suitable donor.

If a suitable donor cannot be found, there are other options, including:

Before the transplant, your doctors will need to prepare your body to receive the new stem cells. This is called the preparative or conditioning regimen. It consists of chemotherapy and radiation given several days before your transplant.Stem cell transplant side effects can be caused by the preparative regimen or by the transplant itself.Your transplant team can help you cope with side effects. Some can be prevented, and most can be treated to help you feel better.

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Stem Cell (Bone Marrow) Transplants - MD Anderson Cancer Center

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What are stem cells?

All of the blood cells in your body - white blood cells, red blood cells, and platelets - start out as young (immature) cells called hematopoietic stem cells. Hematopoietic means blood-forming.These are very young cells that are not fully developed. Even though they start out the same, these stem cells can mature into any type of blood cell, depending on what the body needs when each stem cell is developing.

Stem cells mostly live in the bone marrow (the spongy center of certain bones). This is where they divide to make new blood cells. Once blood cells mature, they leave the bone marrow and enter the bloodstream. A small number of the immature stem cells also get into the bloodstream. These are called peripheral blood stem cells.

Stem cells make red blood cells, white blood cells, and platelets. We need all of these types of blood cells to keep us alive. For these blood cells to do their jobs, you need to have enough of each of them in your blood.

Red blood cells carry oxygen away from the lungs to all of the cells in the body. They bring carbon dioxide from the cells back to the lungs to be exhaled. A blood test called a hematocrit shows how much of your blood is made up of RBCs. The normal range is about 35% to 50% for adults. People whose hematocrit is below this level have anemia. This can make them look pale and feel weak, tired, and short of breath.

White blood cells help fight infections caused by bacteria, viruses, and fungi. There are different types of WBCs.

Neutrophilsare the most important type in fighting infections. They are the first cells to respond to an injury or when germs enter the body. When they are low, you have a higher risk of infection. The absolute neutrophil count (ANC) is a measure of the number of neutrophils in your blood. When your ANC drops below a certain level, you have neutropenia. The lower the ANC, the greater the risk for infection.

Lymphocytesare another type of white blood cell. There are different kinds of lymphocytes, such as T lymphocytes (T cells), B lymphocytes (B cells), and natural killer (NK) cells. Some lymphocytes make antibodies to help fight infections. The body depends on lymphocytes to recognize its own cells and reject cells that dont belong in the body, such as invading germs or cells that are transplanted from someone else.

Platelets are pieces of cells that seal damaged blood vessels and help blood to clot, both of which are important in stopping bleeding. A normal platelet count is usually between 150,000/cubic mm and 450,000/cubic mm, depending on the lab that does the test. A person whose platelet count drops below normal is said to have thrombocytopenia, and may bruise more easily, bleed longer, and have nosebleeds or bleeding gums. Spontaneous bleeding (bleeding with no known injury) can happen if a persons platelet count drops lower than 20,000/mm3. This can be dangerous if bleeding occurs in the brain, or if blood begins to leak into the intestines or stomach.

You can get more information on blood counts and what the numbers mean in Understanding Your Lab Test Results.

Depending on the type of transplant thats being done, there are 3 possible sources of stem cells to use for transplants:

Bone marrow is the spongy liquid tissue in the center of some bones. It has a rich supply of stem cells, and its main job is to make blood cells that circulate in your body. The bones of the pelvis (hip) have the most marrow and contain large numbers of stem cells. For this reason, cells from the pelvic bone are used most often for a bone marrow transplant. Enough marrow must be removed to collect a large number of healthy stem cells.

The bone marrow is harvested (removed) while the donor is under general anesthesia (drugs are used to put the patient into a deep sleep so they dont feel pain). A large needle is put through the skin on the lower back and into the back of the hip bone. The thick liquid marrow is pulled out through the needle. This is repeated until enough marrow has been taken out. (For more on this, see Whats It Like to Donate Stem Cells?)

The harvested marrow is filtered, stored in a special solution in bags, and then frozen. When the marrow is to be used, its thawed and then put into the patients blood through a vein, just like a blood transfusion. The stem cells travel to the bone marrow, where they engraft or take and start to make blood cells. Signs of the new blood cells usually can be measured in the patients blood tests in a few weeks.

Normally, not many stem cells are found in the blood. But giving stem cell donors shots of hormone-like substances called growth factors a few days before the harvest makes their stem cells grow faster and move from the bone marrow into the blood.

For a peripheral blood stem cell transplant, the stem cells are taken from blood. A special thin flexible tube (called a catheter) is put into a large vein in the donor and attached to tubing that carries the blood to a special machine. The machine separates the stem cells from the rest of the blood, which is returned to the donor during the same procedure. This takes several hours, and may need to be repeated for a few days to get enough stem cells. The stem cells are filtered, stored in bags, and frozen until the patient is ready for them. (For more on this, see Whats It Like to Donate Stem Cells?)

When theyre given to the patient, the stem cells are put into a vein, much like a blood transfusion. The stem cells travel to the bone marrow, engraft, and then start making new, normal blood cells. The new cells are usually found in the patients blood in about 4 weeks.

The blood of newborn babies normally has large numbers of stem cells. After birth, the blood thats left behind in the placenta and umbilical cord (known as cord blood) can be taken and stored for later use in a stem cell transplant. Cord blood can be frozen until needed. A cord blood transplant uses blood that normally is thrown out after a baby is born. After the baby is born, specially trained members of the health care team make sure the cord blood is carefully collected. The baby is not harmed in any way. More information on donating cord blood can be found in Whats It Like to Donate Stem Cells?

Even though the blood of newborns has large numbers of stem cells, cord blood is only a small part of that number. So, a possible drawback of cord blood is the smaller number of stem cells in it. But this is partly balanced by the fact that each cord blood stem cell can form more blood cells than a stem cell from adult bone marrow. Still, cord blood transplants can take longer to take hold and start working. Cord blood is given into the patients blood just like a blood transfusion.

Some cancers start in the bone marrow and others can spread to it. Cancer attacks the bone marrow, causing it to make too many of some cells that crowd out others, or causing it to make cells that arent healthy and don't work like they should. For these cancers to stop growing, they need bone marrow cells to work properly and start making new, healthy cells.

Most of the cancers that affect bone marrow function are leukemias, multiple myeloma, and lymphomas. All of these cancers start in blood cells. Other cancers can spread to the bone marrow, which can affect how blood cells function, too.

For certain types of leukemia, lymphoma, and multiple myeloma, a stem cell transplant can be an important part of treatment. The goal of the transplant is to wipe out the cancer cells and the damaged or non-healthy cells that aren't working right, and give the patient new, healthy stem cells to start over."

Stem cell transplants are used to replace bone marrow cells that havebeen destroyed by cancer or destroyed by the chemo and/or radiation used to treat the cancer.

There are different kinds of stem cell transplants. They all use very high doses of chemo (sometimes along with radiation) to kill cancer cells. But the high doses can also kill all the stem cells a person has and can cause the bone marrow to completely stop making blood cells for a period of time. In other words, all of a person's original stem cells are destroyed on purpose. But since our bodies need blood cellsto function, this is where stem cell transplants come in. The transplanted stem cells help to "rescue" the bone marrow by replacingthe bodys stem cells that have been destroyedby treatment. So, transplanting the healthy cellslets doctors use much higher doses of chemo to try to kill all of the cancer cells, and the transplanted stem cells can grow into healthy, mature blood cells that work normally and reproduce cells that are free of cancer.

There's another way astem cell transplant can work, if it's a transplant that uses stem cells from another person (not the cancer patient). In these cases, the transplant can help treat certain types of cancer in a way other than just replacing stem cells. Donated cells can often find and kill cancer cells better than the immune cells of the person who had the cancer ever could. This is called the graft-versus-cancer or graft-versus-leukemia effect. The "graft" is the donated cells. The effect means that certain kinds of transplants actually help kill off the cancer cells, along with rescuing bone marrow and allowing normal blood cells to develop from the stem cells.

Although a stem cell transplant can help some patients, even giving some people a chance for a cure, the decision to have a transplant isnt easy. Like everything in your medical care, you need to be the one who makes the final choice about whether or not youll have a stem cell transplant. Transplant has been used to cure thousands of people with otherwise deadly cancers. Still, there arepossible risks and complications that can threaten life, too. People have died from complications of stem cell transplant. The expected risks and benefits must be weighed carefully before transplant.

Your cancer care team will compare the risks linked with the cancer itself to the risks of the transplant. They may also talk to you about other treatment options or clinical trials. The stage of the cancer, patients age, time from diagnosis to transplant, donor type, and the patients overall health are all part of weighing the pros and cons before making this decision.

Here are some questions you might want to ask. For some of these, you may need to talk to the transplant team or the people who work with insurance and payments for the doctors office and/or the hospital:

Be sure to express all your concerns and get answers you understand. Make sure the team knows whats important to you, too. Transplant is a complicated process. Find out as much as you can and plan ahead before you start.

Its important to know the success rate of the planned transplant based on your diagnosis and stage in treatment, along with any other conditions that might affect you and your transplant. In general, transplants tend to work better if theyre done in early stages of disease or when youre in remission, when your overall health is good. Ask about these factors and how they affect the expected outcomes of your transplant or other treatment.

Many people get a second opinion before they decide to have a stem cell transplant. You may want to talk to your doctor about this, too. Also, call your health insurance company to ask if they will pay for a second opinion before you go. You might also want to talk with them about your possible transplant, and ask which transplant centers are covered by your insurance.

Stem cell transplants cost a lot, and some types cost more than others. For example, getting a donor's cells costs more than collecting your own cells. And, different drug and radiation treatments used to destroy bone marrow can have high costs. Some transplants require more time in the hospital than others, and this can affect cost. Even though there are differences, stem cell transplants can cost hundreds of thousands of dollars.

A transplant (or certain types of transplants) is still considered experimental for some types of cancer, especially some solid tumor cancers, so insurers might not cover the cost.

No matter what illness you have, its important to find out what your insurer will cover before deciding on a transplant, including donor match testing, cell collection, drug treatments, hospital stay, and follow-up care. Go over your transplant plan with them to find out whats covered. Ask if the doctors and transplant team you plan to use are in their network, and how reimbursement will work. Some larger insurance companies have transplant case managers. If not, you might ask to speak with a patient advocate. You can also talk with financial or insurance specialists at your doctors office, transplant center, and hospital about what expenses you are likely to have. This will help you get an idea of what you might have to pay in co-pays and/or co-insurance.

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How Stem Cell and Bone Marrow Transplants Are Used to Treat Cancer

Bone Marrow Stem Cells Comments Off on How Stem Cell and Bone Marrow Transplants Are Used to Treat Cancer | October 13th, 2024

Imagine finding out that your bone marrow or blood stem cells could save the life of someone who needed it even a complete stranger. Memorial Sloan Kettering Cancer Center (MSK) nurse Grace Yang, RN, received such a call in March 2024.

This is definitely something I was never expecting to happen to me, Yang says. But because I work in the Bone Marrow Transplant [BMT] Service, I knew the impact it could have on somebody elses life. It felt like a privilege to be able to help in a different way. Yang works as an office practice nurse for BMT and cellular therapy specialist Heather Landau, MD.

Stem cell and bone marrow donations can offer people with blood cancer and other blood diseases the best chance for a cure. There is an urgent need for more donors between the ages of 18 and 40, especially donors of non-European and mixed ancestry. Yang, who is of Asian ancestry, was 29 when she donated.

You may wonder how to donate, whether donating bone marrow or blood stem cells is painful, and whats involved in bone marrow and stem cell transplantation procedures. Heres what you need to know.

First, some background: Transplanting donor stem cells that form new blood cells in a patient is a lifesaving treatment for many people with blood cancers like leukemia and lymphoma,as well as some other blood diseases. Contrary to what many people might think, the cells used in the transplant are usually collected from the donors bloodstream. Only on rare occasions are the stem cells taken from the bone marrow.

These donor cells are needed because before receiving a transplant, patients are given chemotherapyand sometimes radiationto wipe out the cancer. These treatments also destroy the patients blood-making cells.So they need healthy blood stem cells to be infused into their body. This transplant procedure enables patients to grow new blood cells and recover from the treatment.

Every year, about 18,000 people in the United States are diagnosed with a life-threatening illness for which a stem cell transplant from a donor is the best treatment option. Unfortunately, only about 30% of those patients have a family member who is the best match. That means that about 12,000 people need to find an unrelated donor.

One way that donors are found is through NMDP, which maintains a registry for connecting unrelatedvolunteer donorswith patientsin need. Unfortunately, many people are reluctant to join this registrybecause they dont realize the process is easier than they think, nor do they fully appreciate the desperate need for donors.

Yang signed up for the NMDP registry through a community drive, before she even worked in the BMT field. More than a decade later, she learned she was a match with a patient. I encourage all the people around me to sign up, she says. They are shocked that its so easy.

Even if a patient has an adult sibling who is the right age to donate, there is only a 1 in 4 chance a sibling will be a perfect match.

Siblings and other family members are often a half match, and this can be a good option for many patients. But for some patients, the best way to maximize the chances of a successful transplant is to find a fully matched donor even one who is unrelated.

There are a lot of misconceptions about donating bone marrow and stem cells, especially that it is a burden or painful.

When Yang first told her parents that she had been matched to a patient in need, she found out that her father had also donated bone marrow to stranger more than 20 years ago. At that time, the process was more complicated. Because of his past experience, her father was a bit concerned about what she might go through, but she explained that thanks to advances in technology, the donation process is much easier than it used to be.

Here is a step-by-step guide:

Because studies have shown that patients receiving blood stem cells from younger donors have a better long-term survival rate, you must be between the ages of 18 and 40 to join the registry.

Joining the registry is simple. Go to http://www.bethematch.org to order a collection test kit that will be sent to your house. The website may also direct you to a local registration drive in your area. Once you get the kit, all you need to do is wipe a cotton swab on the inside of your cheek, seal it in a provided container, and mail it back.

You will be contacted if you are a full match or a partial match for a patient in need of a bone marrow or stem cell transplant. Congratulations! Your cells may be the best option to save that persons life.

Several additional steps will be needed to confirm that a transplant with your cells is likely to be successful. These include filling out a health questionnaire, having additional blood tests, and undergoing a physical examination.

If testing confirms that you are a suitable donor, your donation will be scheduled for a time that works for you and for the patients treatment schedule. Depending on where you live, you may need to travel to one of the specialized facilities that collects the stem cells from blood or bone marrow. If you need to travel, your expenses will be covered by NMDP.

Yang traveled to Chicago to make her donation, and the NMDP not only arranged her trip and paid for everything, but it also paid for her sister to travel with her so she didnt have to go alone.

Thanks to procedures developed over the past few decades, 90% of the time the stem cells needed for the transplant are taken from the blood, not the bone marrow. This process is much easier for donors because it does not require surgery.

With stemcell donation from the blood, there is little pain. It is very similar to donating blood platelets. The main difference is that for a few days ahead of time, donors need to receive an injection of a drug called filgrastim (Neupogen), which stimulates the bone marrow to produce extra blood-forming stem cells. Donors may experience some bone pain or a low-grade fever while taking filgrastim, but the side effects usually are not severe and go away after the donation process is complete.

Most people are able to give themselves injections of filgrastim at home, so they dont need to go to the doctor every day.

On the day of the donation, the donor is hooked up to what is called an apheresis machine. The blood is collected from one arm, sent through a machine that removes the stem cells, and then returned to the other arm. Other than the initial needle prick, it is not a painful experience.

The process takes several hours, during which donors often read or watch movies. It may be necessary for donors to return for a second day, depending on how many cells are retrieved.

For Yang, the donation took about 3 hours. We started in the morning, and I was done before lunch, she says. The nurses did a great job of making me feel comfortable and checked on me often throughout the process.

In only about 10% of cases, doctors may recommend the patient receive a bone marrow donation requiring a surgical procedure. Donors are placed under general anesthesia, while bone marrow is removed from small holes drilled into their pelvic bones.

This procedure takes an hour or two, and usually donors can go home that same day.

If you have donated stem cells from your blood, you may feel tired for a few days, but many donors feel no effects at all the next day.

If you have donated bone marrow, you will probably have some pelvic and hip pain, as well as some bruising, for a few days after the procedure. These aches and pains can be controlled with over-the-counter pain medications like Advil and Tylenol. Most people can go back to regular activities right away, but your medical team can provide more details for specific activities.

The process by which the donor and recipient are matched is called HLA (human leukocyte antigen) typing. Its not the same as blood type.Instead, it has to do with the immune proteins that we all inherit at birth from both of our parents. The immune system uses these proteins to understand which cells belong to your body and which do not. A perfect match means that 8 out of 8 markers are the same.

Matching is not related to gender, so your donation can go to someone of any gender as long as the HLA markers align.

Yang has not yet learned anything about the patient who received her cells, but hopes to in the coming months. I just feel so lucky that I was able to do something amazing for somebody else, she says.

Not everyone who needs a donor is able to find one who is fully matched. A patients best chance of finding a donor is someone within their own ethnic group. Members of certain ethnic groups, including those of Latin American, Asian, African, and Middle Eastern ancestry, have a harder time finding a match. These groups tend to be underrepresented in public registries.

For example, for people of Latin American descent, the odds of finding a matched donor in a public registry are less than 50%. For Black patients, the odds are only about 30%. It may be even harder for people of mixed ethnic backgrounds to find donors because their HLA makeup can be more complex.

This makes it especially important for people from these underrepresented ethnic groups, as well as those who have mixed ancestry, to join a public registry like NMDP.

For patients who are unable to find a fully matched donor, there are other options. These include:

These treatments can offer patients very good outcomes, but in some cases its better to have a donor who is a perfect match.

Yang says even though she works as a BMT nurse, she still had questions throughout the donation process. Everyone at NMDP is great about addressing any concerns you may have about the process, and they have many great resources, she says. Any time I have the opportunity to talk to someone about this, I encourage them to get involved.

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Donating Bone Marrow and Stem Cells: The Process and What To Expect

Bone Marrow Stem Cells Comments Off on Donating Bone Marrow and Stem Cells: The Process and What To Expect | October 13th, 2024

Diseases like leukemia, lymphoma, multiple myeloma or bone marrow failure syndromes can affect bone marrow. Bone marrow is a spongy tissue inside bones that is rich in stem cells and helps to produce blood and immune cells. Healthy stem cells are often needed to treat these marrow-impacting diseases. This is why stem cell transplant and bone marrow transplant are often used interchangeably, the main difference being the method of collection of the stem cells.

In some cases especially for some blood cancers a person can use stem cells from their own body to facilitate giving higher doses of chemotherapy in an attempt to cure the disease. This is called an autologous stem cell transplant. The other option, especially when a recipients bone marrow is already compromised, requires a donor to provide healthy stem cells, which is called an allogeneic stem cell transplant.

William Hogan, M.B., B.Ch., is a consultant hematologist and director of the Mayo Clinic Blood and Bone Marrow Transplant Program. Dr. Hogan says that about one-quarter of transplant recipients at Mayo Clinic receive an allogeneic transplant, which means a donors immune system is used in a life-sustaining and curative therapy to help eradicate disease.

If you are selected (as a bone marrow donor), you might be a critically important part of a persons treatment, he says.

To help someone with an allogenic stem cell transplant, you can donate stem cells from your:

Health care providers determine which type of donation is best for a person on a case-by-case basis. Factors that influence this decision can include the type of disease, the degree of donor matching, and other patient characteristics like age and remission status.

Dr. Hogan says that in the past, family members especially fully matched siblings were considered the best option to donate bone marrow. But the fact is that a majority of people who need a bone marrow transplant dont have a family member who is a full match.

Additionally, cancers that require bone marrow transplants frequently affect older adults. Older adult sibling donors are more likely to have co-morbidities that can put the donor at risk and can increase the risk of complications with the recipient.

For these reasons, the National Marrow Donor Program manages a registry of bone marrow donors that can be matched with unrelated recipients.

To help increase the long-term survival rate of a bone marrow recipient, the National Marrow Donor Program prefers healthy donors who are 18 to 35 years old, although Dr. Hogan says that older donors can be an option in select circumstances. He says that determining a good match for a bone marrow transplant includes looking at a donors proteins in cells called human leukocyte antigens (HLA) and blood type. Optimal donors will match HLA and blood type and be free of genetic and infectious diseases.

Being a donor does require a time commitment, often 20 to 30 hours over 4 to 6 weeks from screening to donation. In terms of financial requirements to be a bone marrow donor through the National Marrow Donor Program, there arent any. All your medical and travel expenses are covered.

The U.S. Health Resources & Services Administration states that even though there are more than 40 million potential bone marrow donors in the world, its harder for people with racially and ethnically diverse backgrounds to find a match.

Getting greater diversity in the bone marrow registry is important, since ethnicity impacts HLA matching to some degree, says Dr. Hogan. We need to ensure that underrepresented minorities have adequate representation. We want to provide better donors for better outcomes.

According to the National Marrow Donor Program, people who need bone marrow are most likely to match with someone of their own ethnic background. The odds of finding a match through the bone marrow donation registry vary based on ethnic background. For example, if a recipient is white, they have a 79% chance of finding a match. If they are Hispanic or Latino, the odds of a match drop to 48%. And for recipients who are Black or African American, the chance of finding a match is just 29%.

If you donate bone marrow, you will undergo surgery. During the surgery, you are under general anesthesia and a needle is inserted into your hip bones to collect the bone marrow. The effects of general anesthesia can include more minor complaints such as a sore throat and nausea, as well as some serious but rare complications.

Aside from the use of anesthesia, other risks of bone marrow donation surgery include:

After the surgery to collect bone marrow, you might experience pain where the needle was inserted when you bend or walk. The pain tends to lessen after the first several days and is usually gone within 6 to 12 weeks.

Dr. Hogan says that there are misconceptions about the pain associated with bone marrow donation. Many donors report that the value of their donation and the contribution to saving somebodys life often outweighs the discomfort of the procedure, he says.

He explains that donation surgery is more involved than a blood draw, but the pain should be well managed, and most donors have a positive experience.

Many people take several days off following bone marrow collection surgery so that they can take rest periods throughout the day and slowly resume normal activities. After the collection, it takes a few weeks for your bone marrow to replenish, and after that, most symptoms like soreness and fatigue should be gone. The total recovery process can typically take 2 to 6 weeks, according to Dr. Hogan.

If you are highly motivated to help others, Dr. Hogan suggests that you start at the National Marrow Donor Programs Be the Match site, where you can learn more about the process to join and what happens if you are selected as a match.

Joining the voluntary registry is a simple process. First, youll answer questions about your medical history in an initial screening. If you qualify, the next step is to swab the inside of your cheek to determine your HLA type. Those two steps are what it takes to join.

Once youve joined the registry, you might not be identified as a match until you opt out or age out when you turn 61. Once youve joined the registry, you can change your mind about being a donor at any time.

Even if you join the registry with the intent of helping a friend or family member, it might turn out that youre a better match for someone you dont know. If you do match, you might be asked to donate either bone marrow or blood, depending on what the recipient needs.

If you are selected as a match, your donation has the power to transform someones life.

Relevant reading

Mayo Clinic The Integrative Guide to Good Health

As Americans seek greater control of their health, explosive growth is taking place in the field of integrative medicine. More and more, people are looking for more natural or holistic ways to maintain good health; they want not only to manage and prevent illness but also to improve their quality

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What to expect as a stem cell or bone marrow donor

Bone Marrow Stem Cells Comments Off on What to expect as a stem cell or bone marrow donor | October 13th, 2024