scholarly journals Embryonic Regulation of the Mouse Hematopoietic Niche

2011 ◽  
Vol 11 ◽  
pp. 1770-1780 ◽  
Author(s):  
Daisuke Sugiyama ◽  
Tomoko Inoue-Yokoo ◽  
Stuart T. Fraser ◽  
Kasem Kulkeaw ◽  
Chiyo Mizuochi ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extrinsic Factors ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Healthy Donors ◽  
Intrinsic Regulation ◽  
Embryonic Regulation ◽  
Hematopoietic Niche ◽  
Transplantation Therapy

Hematopoietic stem cells (HSCs) can differentiate into several types of hematopoietic cells (HCs) (such as erythrocytes, megakaryocytes, lymphocytes, neutrophils, or macrophages) and also undergo self-renewal to sustain hematopoiesis throughout an organism's lifetime. HSCs are currently used clinically as transplantation therapy in regenerative medicine and are typically obtained from healthy donors or cord blood. However, problems remain in HSC transplantation, such as shortage of cells, donor risks, rejection, and graft-versus-host disease (GVHD). Thus, increased understanding of HSC regulation should enable us to improve HSC therapy and develop novel regenerative medicine techniques. HSC regulation is governed by two types of activity: intrinsic regulation, programmed primarily by cell autonomous gene expression, and extrinsic factors, which originate from so-called “niche cells” surrounding HSCs. Here, we focus on the latter and discuss HSC regulation with special emphasis on the role played by niche cells.

Malignant Myeloma Cells Impair Phenotype and Function of stem and Progenitor Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1799-1799
Author(s):  
Ingmar Bruns ◽  
Sebastian Büst ◽  
Akos G. Czibere ◽  
Ron-Patrick Cadeddu ◽  
Ines Brückmann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Progenitor Cells ◽  
Plasma Cells ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Healthy Donors ◽  
Stem And Progenitor Cells

Abstract Abstract 1799 Poster Board I-825 Multiple myeloma (MM) patients often present with anemia at the time of initial diagnosis. This has so far only attributed to a physically marrow suppression by the invading malignant plasma cells and the overexpression of Fas-L and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by malignant plasma cells triggering the death of immature erythroblasts. Still the impact of MM on hematopoietic stem cells and their niches is scarcely established. In this study we analyzed highly purified CD34+ hematopoietic stem and progenitor cell subsets from the bone marrow of newly diagnosed MM patients in comparison to normal donors. Quantitative flowcytometric analyses revealed a significant reduction of the megakaryocyte-erythrocyte progenitor (MEP) proportion in MM patients, whereas the percentage of granulocyte-macrophage progenitors (GMP) was significantly increased. Proportions of hematopoietic stem cells (HSC) and myeloid progenitors (CMP) were not significantly altered. We then asked if this is also reflected by clonogenic assays and found a significantly decreased percentage of erythroid precursors (BFU-E and CFU-E). Using Affymetrix HU133 2.0 gene arrays, we compared the gene expression signatures of stem cells and progenitor subsets in MM patients and healthy donors. The most striking findings so far reflect reduced adhesive and migratory potential, impaired self-renewal capacity and disturbed B-cell development in HSC whereas the MEP expression profile reflects decreased in cell cycle activity and enhanced apoptosis. In line we found a decreased expression of the adhesion molecule CD44 and a reduced actin polymerization in MM HSC by immunofluorescence analysis. Accordingly, in vitro adhesion and transwell migration assays showed reduced adhesive and migratory capacities. The impaired self-renewal capacity of MM HSC was functionally corroborated by a significantly decreased long-term culture initiating cell (LTC-IC) frequency in long term culture assays. Cell cycle analyses revealed a significantly larger proportion of MM MEP in G0-phase of the cell cycle. Furthermore, the proportion of apoptotic cells in MM MEP determined by the content of cleaved caspase 3 was increased as compared to MEP from healthy donors. Taken together, our findings indicate an impact of MM on the molecular phenotype and functional properties of stem and progenitor cells. Anemia in MM seems at least partially to originate already at the stem and progenitor level. Disclosures Off Label Use: AML with multikinase inhibitor sorafenib, which is approved by EMEA + FDA for renal cell carcinoma.

scholarly journals JAK2V617F mutant megakaryocytes contribute to hematopoietic aging in a murine model of myeloproliferative neoplasm

2021 ◽  
Author(s):  
Sandy Lee ◽  
Helen Wong ◽  
Melissa Castiglione ◽  
Malea Murphy ◽  
Kenneth Kaushansky ◽  
...  
Keyword(s):  
Murine Model ◽  
Matched Control ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Rna Expression Profiling ◽  
Old Mice ◽  
Hallmark Feature ◽  
Hematopoietic Niche

Megakaryocytes (MKs) is an important component of the hematopoietic niche. Abnormal MK hyperplasia is a hallmark feature of myeloproliferative neoplasms (MPNs). The JAK2V617F mutation is present in hematopoietic cells in a majority of patients with MPNs. Using a murine model of MPN in which the human JAK2V617F gene is expressed specifically in the MK lineage, we show that the JAK2V617F-bearing MKs promote hematopoietic stem cell (HSC) aging, manifesting as myeloid-skewed hematopoiesis with an expansion of CD41+ HSCs, a reduced engraftment and self-renewal capacity, and a reduced differentiation capacity. HSCs from 2yr old mice with JAK2V617F-bearing MKs were more proliferative and less quiescent than HSCs from age-matched control mice. Examination of the marrow hematopoietic niche reveals that the JAK2V617F-bearing MKs not only have decreased direct interactions with hematopoietic stem/progenitor cells during aging, but also suppress the vascular niche function during aging. Unbiased RNA expression profiling reveals that HSC aging has a profound effect on MK transcriptomic profiles, while targeted cytokine array shows that the JAK2V617F-bearing MKs can alter the hematopoietic niche through increased levels of pro-inflammatory and anti-angiogenic factors. Therefore, as a hematopoietic niche cell, MKs represent an important connection between the extrinsic and intrinsic mechanisms for HSC aging.

scholarly journals Tooth Regenerative Therapy, Approached from Organogenesis

2007 ◽  
Vol 19 (5) ◽  
pp. 506-511
Author(s):  
Kazuhisa Nakao ◽  
◽  
Takashi Tsuji ◽  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Artificial Organs ◽  
Therapeutic System ◽  
Partial Loss ◽  
Organ Function ◽  
Hematopoietic Stem ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy ◽  
Organ Replacement

Regenerative medicine is expected to be a novel therapeutic system in this century [1-3]. The human body consists of 200 cell species generated from immature stem cells. In the 1990s, a treatment transplanting hematopoietic stem cells to replace all blood cells was established and successfully cured leukemia [4]. With this as a model, stem cell transplantation therapy is being developed to restore the partial loss of organ function [5, 6]. The ultimate goal of regenerative medicine is to replace loss or damaged organs with artificial organs, so-called organ replacement therapy. Technical development to produce “tissues” made of a single cell species modeled on skin, bone, heart muscle, and cornea is advancing, but little development of organs per se has been attempted. In the sections that follow, we discuss why and explain how we are trying with the problems of “tooth regeneration.”

scholarly journals Senescent Mesenchymal Stem Cells Present at the Early Post Allogeneic Hematopoietic Stem Cell Transplantation Period Are Associated with an Increased Incidence of Acute Graft-Versus Host Disease and Increased Plasma Levels of Fas Ligand

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2116-2116
Author(s):  
Daniel Rivera ◽  
Lika Osugui ◽  
Sandra Muntion ◽  
Miguel Alcoceba ◽  
Concepcion Rodriguez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Board Of Directors ◽  
Fas Ligand ◽  
Ex Vivo ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Healthy Donors

Abstract Introduction Mesenchymal stem cells (MSC) are a key component of the hematopoietic niche. In the allogeneic hematopoietic stem cell transplantation (allo-HSCT) setting, the bone marrow stroma, and thus, their MSC remain of host origin. In a preliminary study we observed that, some patients at the early post allo-HSCT period, presented senescent bone marrow (BM) MSC, a finding that has not been previously described nor studied. The aims of our current study were: a) To multiparametrically characterize BM MSC at the early post allo-HSCT period (day +21). b) To confirm senescence of MSC and correlate with clinical and biological parameters (including biomarkers). c) To compare these cells with those from healthy donors. Methods We obtained BM samples on the day +21 post allo-HSCT from 136 patients. MSC were isolated, ex-vivo expanded and characterized, according to the criteria of the International Society for Cellular Therapy. We also obtained samples from peripheral blood at same day +21, for the study of biomarkers, which were analyzed by Luminex technique. The data were correlated with information from complete blood counts (CBC), and the morphological study of the bone marrow the same day. MSC from healthy donors were used as control. Results Patient baseline and transplant related characteristics are detailed in table 1. MSC were expanded ex-vivo showing normal growth, which were cryopreserved in passage 3 in the 33% (n=45/136) of the patients (Group-MSC-N). On the other hand, the remaining 67% (n=91/136), MSC showed premature signs of senescence, thus, not reaching to passage 1 (Group-MSC-S). Full BM chimerism on day+21 was seen in both groups (p=0.03). Concerning acute graft versus-host disease (aGVHD), in the Group-MSC-S, the incidence was 73% compared to 44% in the Group-MSC-N (p=0.001). The median time of the onset of aGVHD was 43 and 37 days respectively (p=0.04). The majority of cases presented with grades I-II in both groups. Plasma levels of biomarkers showed increased levels of Fas Ligand in the Group-MSC-S (p=0.009). There were no statistically significant differences regarding mortality nor relapse rates. Conclusions Bone marrow Mesenchymal stem cells may be severely damaged in some allo-HSCT recipients early after transplantation (day+21). This fact strongly correlates with the risk of development of acute GVHD. Disclosures Díez-Campelo: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Reconstructing the Human Hematopoietic Niche: Opportunities for Studying Normal and Malignant Hematopoiesis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3412-3412
Author(s):  
Richard W Groen ◽  
Willy A Noort ◽  
Reinier Raymakers ◽  
Henk-Jan Prins ◽  
Linda Aalders ◽  
...  
Keyword(s):  
Therapy Resistance ◽  
Human Bone ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Poor Risk Patient ◽  
Human Cd34 ◽  
Mouse Tissues ◽  
Novel Scaffold ◽  
Hematopoietic Niche ◽  
Good Risk

Abstract Abstract 3412 Interactions with the hematopoietic niche in the bone marrow (BM) microenvironment are essential for hematopoietic stem cell (HSC) self-renewal. In addition, in hematological malignancies this niche is considered to serve as a sanctuary site for leukemic stem cells during chemotherapy, and to contribute to disease relapse. Although many advances have been made in understanding how the niche regulates HSC self-renewal and confers therapy resistance, most of this knowledge is based on genetic loss- or gain-of-function murine models. Since these models do not recapitulate the human physiology, there is a need for models that more closely resemble the human niche. Here, we describe a unique humanized model, which implements a novel scaffold-based technology for generating a human bone environment in RAG2−/−gc−/−-mice. Inoculation of these mice with normal human CD34+ hematopoietic progenitor cells, isolated from umbilical cord blood, resulted in homing to the human bone environment and the generation of human hematopoietic cells of distinct lineages, but more importantly also the engraftment of CD34+ cells themselves. In a next series of experiments the supportive nature of the humanized niche was further investigated with patient-derived acute myeloid leukemia (pAML) and multiple myeloma (pMM) cells, two hematopoietic malignancies that are highly dependent on the BM microenvironment for survival and growth. Inoculation of the humanized mice with pAML cells, obtained from a poor-risk patient (M1; complex karyotype) or cells from a good risk AML patient (M4; inv(16)) revealed the ability of the reconstructed human bone environment to support outgrowth of the leukemia with the cells having a similar phenotype as those from the patient sample. Interestingly, engraftment of good risk AML samples, including inv(16), has been reported to be very difficult in the NOD/SCID-based AML xenotransplant model. The humanized model that we developed was further substantiated by the ability to support the outgrowth of pMM from 7 out of 7 patients. MM is a hematological malignancy that fails to grow in mouse tissues without extra support, e.g. fetal human bone chips. Moreover, the outgrowth of pMM in our humanized model is accompanied by an increase in osteoclast activity, indicating the presence of bone resorption, one of the most relevant clinical sequelae of MM. In addition, by gene-marking pMM cells with luciferase and using bioluminescent imaging, we were able to follow myeloma outgrowth in time. Treatment of pMM-bearing mice with identical drugs as given to the patients showed that the pMM cells growing in the humanized environment in the mice responded similar as the MM patients. Hence, our model allows, for the first time, to investigate essential interactions within the human BM microenvironment for the development of normal and malignant hematopoiesis and thus for therapy development. Disclosures: de Bruijn: Xpand Biotechnology BV: Employment. Weers:Genmab BV: Employment. Parren:Genmab BV: Employment.

FG-4497, a Pharmacological Stabilizer of HIF-1α Protein, Synergistically Enhances Hematopoietic Stem Cells (HSC) Mobilization in Response to G-CSF and Plerixafor

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 216-216 ◽  
Author(s):  
Catherine E Forristal ◽  
Bianca Nowlan ◽  
Valerie Barbier ◽  
Ingrid G Winkler ◽  
Gail Walkinshaw ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Cell Types ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Prolyl Hydroxylases ◽  
Treatment Groups ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
O2 Concentration

Abstract Abstract 216 Up to 5% allogeneic healthy donors and up to 40–60% of chemotherapy-treated patients in autologous setting, fail to reach minimal threshold of 2×106 blood CD34+cells/kg in response to G-CSF, precluding transplantation. Plerixafor, a small inhibitor of the chemokine receptor CXCR4, used for 4 days in combination with G-CSF enables this minimal threshold to be reached in up to 60% patients who previously failed to mobilise in response to G-CSF alone. However, the remaining 40% of patients who failed to mobilise in response to G-CSF alone, still fail to mobilize adequately with G-CSF + Plerixafor. In an attempt to further boost HSC mobilization in response to combinations of G-CSF and Plerixafor, we have investigated the role of the hypoxia-sensing pathway in HSC mobilization. HIF-1α (Hypoxia-inducible factor-1α) controls HSC proliferation and self-renewal in poorly perfused hypoxic bone marrow (BM) niches where very quiescent HSC with highest self-renewal potential reside. When O2 concentration is above 2% in the cell microenvironment, HIF-1α protein is rapidly hydroxylated on Pro residues by prolyl hydroxylases PHD1-3. This recruits the E3 ubiquitin ligase VHL, which targets HIF-1α to rapid proteasomal degradation. When O2concentration is below 2% (hypoxia), PHDs are inactive; HIF-1α protein is stabilized, associates with its β subunit ARNT, translocates to the nucleus and activates of transcription and hypoxia-responsive genes. In this study, we have investigated the effect of pharmacological stabilization of HIF-1α protein on HSC mobilization in mice using the HIF-PHD inhibitor FG-4497. We report that FG-4497 treatment stabilizes HIF-1α protein in mouse BM. We find that FG-4497 synergizes with G-CSF and Plerixafor to enhance HSC mobilization. C57/Bl6 mice were in 4 treatment groups: (G) 250μg/kg/day G-CSF alone for 2 days; (GF) G-CSF for 2 days + 20mg/kg/day FG-4497 for 3 days; (GP) G-CSF for 2 days together with16mg/kg Plerixafor 1 hour prior harvest; (GPF) G-CSF together with Plerixafor and FG-4497 with same dosing as above. Mobilization of colony-forming cells (CFC), phenotypic Lin-CD41-Sca1+Kit+CD48-CD150+ HSC, and functional HSC in long-term competitive transplantation assays were measured. Mice in the GF group (G-CSF + FG-4497) mobilized CFC to the blood 4-fold and phenotypic HSC 3-fold more than mice mobilized with G-CSF alone (p<0.005), whereas FG-4497 alone had a poor mobilizing effect. This demonstrates synergy between G-CSF and PHD inhibition. Expectedly, Plerixafor enhanced mobilization of CFC 10-fold and phenotypic HSC 2-fold in response to G-CSF (p<0.005). Most interestingly, addition of FG-4497 boosted 4-fold mobilization of CFC and phenotypic HSC in response to G-CSF+Plerixafor (p<0.005). This was confirmed in competitive repopulation assays following transplantation of 20μL mobilized blood in competition with 2×105BM cells from congenic donors. CD45.2/CD45.1 chimerism showed that combination of G-CSF+Plerixafor+FG-4497 mobilized competitive repopulating HSC 6-fold more than G-CSF+Plerixafor (p<0.005), the best mobilizing cocktail used in the clinic currently. To determine which cell types drive HSC mobilization in a HIF-1α-dependant manner, we crossed HIF1αflox/floxmice with osxCre (HIF-1α gene deletion in osteoprogenitors), LysMCre (deletion in myeloid cells), or with SclCreER mice (tamoxifen-induced deletion in HSC). While studies in LysMCre and SclCreER mice are ongoing, we find that deletion of HIF-1α gene in osteoprogenitors (osxCre mice) decreased 2.5-fold the number of CFU/mL blood following 2 and 3 days treatment with G-CSF. This suggests that HIF-1α in osteoprogenitors and their osteoblastic progenies is necessary for optimal mobilization in response to G-CSF. In conclusion, our data highlight the importance of HIF-1α in HSC mobilization and provide a novel therapeutic strategy for increasing HSC mobilization above levels obtained with combinations of G-CSF and Plerixafor. Thus PHD inhibitors could be useful agents in patients who still fail to mobilize in response to G-CSF and plerixafor. Disclosures: Walkinshaw: Fibrogen Inc.: Employment, Equity Ownership.

scholarly journals Decellularized Wharton jelly matrix: a biomimetic scaffold for ex vivo hematopoietic stem cell culture

2019 ◽  
Vol 3 (7) ◽  
pp. 1011-1026 ◽  
Author(s):  
Dandan Li ◽  
Grace Chiu ◽  
Brea Lipe ◽  
Richard A. Hopkins ◽  
Jacquelyn Lillis ◽  
...  
Keyword(s):  
Culture System ◽  
Ex Vivo ◽  
Cxcr4 Expression ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Megakaryocytic Differentiation ◽  
Cd34 Cells ◽  
Hematopoietic Niche

Abstract Hematopoietic stem progenitor cells (HSPCs) reside in the bone marrow (BM) hematopoietic “niche,” a special 3-dimensional (3D) microenvironment that regulates HSPC self-renewal and multipotency. In this study, we evaluated a novel 3D in vitro culture system that uses components of the BM hematopoietic niche to expand umbilical cord blood (UCB) CD34+ cells. We developed this model using decellularized Wharton jelly matrix (DWJM) as an extracellular matrix (ECM) scaffold and human BM mesenchymal stromal cells (MSCs) as supporting niche cells. To assess the efficacy of this model in expanding CD34+ cells, we analyzed UCB CD34+ cells, following culture in DWJM, for proliferation, viability, self-renewal, multilineage differentiation, and transmigration capability. We found that DWJM significantly expanded UCB HSPC subset. It promoted UCB CD34+ cell quiescence, while maintaining their viability, differentiation potential with megakaryocytic differentiation bias, and clonogenic capacity. DWJM induced an increase in the frequency of c-kit+ cells, a population with enhanced self-renewal ability, and in CXCR4 expression in CD34+ cells, which enhanced their transmigration capability. The presence of BM MSCs in DWJM, however, impaired UCB CD34+ cell transmigration and suppressed CXCR4 expression. Transcriptome analysis indicated that DWJM upregulates a set of genes that are specifically involved in megakaryocytic differentiation, cell mobility, and BM homing. Collectively, our results indicate that the DWJM-based 3D culture system is a novel in vitro model that supports the proliferation of UCB CD34+ cells with enhanced transmigration potential, while maintaining their differentiation potential. Our findings shed light on the interplay between DWJM and BM MSCs in supporting the ex vivo culture of human UCB CD34+ cells for use in clinical transplantation.

scholarly journals Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease

Blood ◽  
2005 ◽  
Vol 106 (8) ◽  
pp. 2903-2911 ◽  
Author(s):  
Emmanuel Zorn ◽  
Haesook T. Kim ◽  
Stephanie J. Lee ◽  
Blair H. Floyd ◽  
Despina Litsa ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Regulatory T Cells ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Healthy Individuals ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Healthy Donors

AbstractChronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation but the immune mechanisms leading to the diverse clinical manifestations of cGVHD remain unknown. In this study, we examined regulatory T cells (Tregs) in 57 transplant recipients (30 with cGVHD and 27 without active cGVHD) and 26 healthy donors. Phenotypic studies demonstrated decreased frequency of CD4+CD25+ T cells in patients with cGVHD compared with patients without cGVHD (P &lt; .001) and healthy individuals (P &lt; .001). Gene expression of Treg transcription factor FOXP3 was reduced in cGVHD patients compared with patients without cGVHD (P = .009) or healthy donors (P = .01). T-cell receptor excision circle (TREC) assays for the evaluation of thymus activity revealed fewer TRECs in both transplant groups compared with healthy donors (P &lt; .001 and P = .02, respectively) although no difference was observed between patients with or without cGVHD (P = .13). When tested in functional assays, Tregs from both patient cohorts and healthy individuals mediated equivalent levels of suppression. Collectively, these studies indicate that patients with active cGVHD have reduced frequencies of Tregs but the function of these cells remains normal. These findings support the development of new strategies to increase the number of Tregs following allogeneic hematopoietic stem cell transplantation to prevent or correct cGVHD. (Blood. 2005; 106:2903-2911)

scholarly journals Pharmacological Regulation of Oxidative Stress in Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Jungwoon Lee ◽  
Yee Sook Cho ◽  
Haiyoung Jung ◽  
Inpyo Choi
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Defense Mechanisms ◽  
Stem Cell Differentiation ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Potential Applications ◽  
Cellular Oxidation

Oxidative stress results from an imbalance between reactive oxygen species (ROS) production and antioxidant defense mechanisms. The regulation of stem cell self-renewal and differentiation is crucial for early development and tissue homeostasis. Recent reports have suggested that the balance between self-renewal and differentiation is regulated by the cellular oxidation-reduction (redox) state; therefore, the study of ROS regulation in regenerative medicine has emerged to develop protocols for regulating appropriate stem cell differentiation and maintenance for clinical applications. In this review, we introduce the defined roles of oxidative stress in pluripotent stem cells (PSCs) and hematopoietic stem cells (HSCs) and discuss the potential applications of pharmacological approaches for regulating oxidative stress in regenerative medicine.

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