Human peripheral blood-born hematosphere as a niche for hematopoietic stem cell expansion

Hur, Jin; Park, Jonghanne; Lee, Sang Eun; Yoon, Chang Hwan; Jang, Jeong Hoon; Yang, Ji Min; Lee, Tae‐Kyu; Choi, Jae Il; Yang, Han Mo; Lee, Eun Ju; Cho, Hyun Jai; Kang, Hyun–Jae; Oh, Byung Hee; Park, Young Bae; Kim, Hyo Soo

doi:10.1038/cr.2011.69

Cited by 11 publications

(14 citation statements)

References 10 publications

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“…Recently, macrophages have been identified as positive regulators for maintenance and retention of HSC niches. 1,5 Our finding that DARC C macrophages show a functional overlap with COX-2 high macrophages corroborates the significance of macrophages in governing HSC quiescence. Further study is required to examine whether the CD82-DARC axis exists in other tissues such as blood vessels, muscle, or heart with an emphasis on tissue-resident stem cells.…”

supporting

confidence: 71%

KAI1(CD82)-DARC(CD234) axis in the stem cell niche

2016

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supporting

confidence: 71%

KAI1(CD82)-DARC(CD234) axis in the stem cell niche

2016

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“…39 Recently, several studies have highlighted the potential of nichesupporting cells. [40][41][42] CD3 + /CD31 + T-cells are required for EPC colony formation during early EPC differentiation. 40 Spheroid culture of blood MNCs potentiates the expansion of circulating blood HSCs.…”

Section: Discussionmentioning

confidence: 99%

“…40 Spheroid culture of blood MNCs potentiates the expansion of circulating blood HSCs. 41 Mesenchymal stem cells support the maintenance of cord blood HSC during long-term ex vivo culture. 42 In the present study, we found that CD34 − cells, particularly macrophages that secrete either VEGF or SDF-1α on activation, might regulate mature EPC differentiation, demonstrated by a novel EPC-CFU assay, suggesting that crosstalk between incorporated EPCs and recruited macrophages plays a critical role in EPC functionality in vitro.…”

Section: Discussionmentioning

confidence: 99%

CD34 Hybrid Cells Promote Endothelial Colony-Forming Cell Bioactivity and Therapeutic Potential for Ischemic Diseases

Lee

Yoo

et al. 2013

ATVB

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Objective-Although endothelial progenitor cells (EPCs) have been reported to promote neovessel formation during vascular injury, the function of supporting cells of EPCs and their interaction with EPCs during EPC isolation remain unclear. Approach and Results-We investigated the functional properties of 2 types of EPCs, also known as endothelial colonyforming cells (ECFCs), CD34− /CD34 + cell-derived ECFCs (hybrid-dECFCs) and CD34 + cell-derived ECFCs (stemdECFCs), isolated using different methods, to elucidate the role of CD34− cell populations as cell-supporting niches. Using EPC colony-forming and insert coculture assays, we found that CD34 − accessory cells dynamically modulate hematopoietic stem cell-derived endothelial cell progenitor commitment via angiogenic cytokines secreted by CD34 − / CD11b + macrophages. On the basis of these findings, we isolated 2 types of ECFCs and investigated their bioactivities. We found that stem-dECFCs showed remarkably retarded cell growth, enhanced senescence, and decreased characteristics of ECFCs, whereas hybrid-dECFCs showed greater proliferative properties but delayed senescence. In a murine hindlimb ischemia model, hybrid-dECFCs showed significantly enhanced blood perfusion, capillary density, transplanted cell survival and proliferation, and angiogenic cytokine secretion compared with stem-dECFCs. In particular, the migratory capacity of hybrid-dECFCs was significantly enhanced, in part mediated via an augmented phosphorylation cascade of focal adhesion kinase and Src, resulting in a highly increased incorporation capacity of hybrid-dECFCs compared with stem-dECFCs. CD34− accessory cells of hybrid-dECFCs might be niche-supporting cells that facilitate cell survival, increase the secretion of angiogenic cytokines, and increase incorporation. Conclusions-This study provided important insight into blood vessel formation and repair in ischemic diseases

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“…In this culture system, a 3D culture of human peripheral blood mononuclear cells (PBMCs) results in spontaneous generation of hematospheres, in which CXCR4 þ CD31 þ myeloid cells are the principal cellular component. Hematosphere culture increases the production of angiogenic niche-supporting cytokines and extracellular matrix molecules, and hematosphere-derived myeloid cells have robust angiogenic capacities and actively participate in vessel formation in vivo (14,15). However, the efficacy of these expanded cells in islet transplantation has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

“…In this context, the spheroid culture method is a reasonable strategy because it can sensitize stem cells to growth factors and provide them sufficient cell-to-cell and cell-to-matrix contacts (12,13). Recently, it has been reported that ex vivo expansion of a highly angiogenic monocyte subset can be achieved through a three-dimensional (3D) culture technique using a high cell density and nonattachable culture system (14,15). In this culture system, a 3D culture of human peripheral blood mononuclear cells (PBMCs) results in spontaneous generation of hematospheres, in which CXCR4 þ CD31 þ myeloid cells are the principal cellular component.…”

Section: Introductionmentioning

confidence: 99%

Improved Revascularization of Islet Grafts Using an Angiogenic Monocyte Subpopulation Derived From Spheroid Culture of Bone Marrow Mononuclear Cells

Jin

Choi

et al. 2015

American Journal of Transplantation

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y Both authors contributed equally to this manuscript.The spheroid culture method is an effective strategy for ex vivo expansion of an autologous therapeutic cell population. We investigated if cotransplantation of bone marrow-derived spheroids (BM-spheroid) formed using 3D culture of BM-derived mononuclear cells (BMMNCs) could improve the posttransplant outcome of islet grafts using a mouse syngeneic marginal mass renal subcapsular islet transplantation model. Using green fluorescent protein transgenic (GFP-Tg) mice, the role of the BM-spheroids and the contribution of vessels derived from donors and recipients in grafted areas were assessed by immunohistochemistry. Compared to fresh BM-MNCs and nonspheroid remnant cells (BM-nonspheroid), the BM-spheroids, mainly composed of CXCR4 þ CD14 þ myeloid cells, showed higher angiogenic capacity, such as in vitro self-formed vessel structures; increased expression of angiogenic and chemoattractive factors; and incorporation into new vessel formation in basement membrane matrix plugs. BM-spheroid cotransplantation with islets improved the posttransplant outcomes in terms of glucose tolerance, serum insulin level, and diabetes reversal rate when compared with cotransplantation of BM-nonspheroids. Immunohistochemistry revealed that cotransplantation of the BM-spheroids increased vessel density, area of grafted endocrine and nonendocrine tissue, and b cell proliferation. In conclusion, cotransplantation of islets and BM-spheroids improved islet function through facilitation of revascularization and an increase in cell proliferation and islet cell mass.Abbreviations: 3D, three-dimensional; Angpt1(2), angiopoiethin-1(2); AUC glu , the area under the glucose curve; BM-MNCs, bone marrow-derived mononuclear cells; BM-nonspheroid, remnant single cells after spheroid culture; BM-spheroid, the spheroid formed by 3D culture of bone marrow-derived mononuclear cells; BS1-lectin, bandeiraea simplicifolia1-lectin; CMDiI, cell tracker dye; Cxcl12, C-X-C motif chemokine 12; DPT, days posttransplantation; EPCs, endothelial progenitor cells; FACS, fluorescence-activated cell sorting; Fgf2, fibroblast growth factor 2 (basic); GFPTg, green fluorescent protein transgenic mice; HUVEC, human umbilical vein endothelial cells; Igf1, insulinlike growth factor 1; IPGTT, intraperitoneal glucose tolerance test; PBMC, peripheral blood mononuclear cells; STZ, streptozotocin; TRITC, tetramethyl rhodamine isothiocyanate; Vegfa, vascular endothelial growth factor A

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Human peripheral blood-born hematosphere as a niche for hematopoietic stem cell expansion

Cited by 11 publications

References 10 publications

KAI1(CD82)-DARC(CD234) axis in the stem cell niche

KAI1(CD82)-DARC(CD234) axis in the stem cell niche

CD34 Hybrid Cells Promote Endothelial Colony-Forming Cell Bioactivity and Therapeutic Potential for Ischemic Diseases

Improved Revascularization of Islet Grafts Using an Angiogenic Monocyte Subpopulation Derived From Spheroid Culture of Bone Marrow Mononuclear Cells

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