Mesenchymal stem cells: A promising candidate in regenerative medicine

Chen, Ye; Shao, Jian‐Zhong; Xiang, Lei; Dong, Xuejun; Zhang, Guorong

doi:10.1016/j.biocel.2008.01.007

Cited by 213 publications

(137 citation statements)

References 17 publications

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“…MSCs have been shown to serve as precursors of most types of these cells. 23 Previously, our group Submitted November 3, 2011; accepted March 25, 2012. Prepublished online as Blood First Edition paper, April 5, 2012; DOI 10.1182 DOI 10.…”

Section: Introductionmentioning

confidence: 99%

“…The inadequacy of the presently used murine systems has recently been highlighted by the finding of distinct genetic abnormalities in the stromal cells from patient with myelodysplatic syndromes and acute myeloid leukemias. 20,21 Mesenchymal stromal cells (MSCs) have been shown to serve as scaffolds for the formation of stem cell niches in BM and exert both positive and negative regulatory effects on the self-renewal, proliferation, and differentiation of HSCs 22,23 However, transplanted human MSCs do not efficiently or consistently engraft at murine sites of hematopoiesis even after intra-BM injection, perhaps because they are competing with a functional murine microenvironment. In the past 2 decades, researchers have attempted to mimic the native BM environment in 2-dimensional culture systems by adding the proper cytokines and growth factors to cell cultures, coculturing HSCs with stromal cells, or both.…”

Section: Introductionmentioning

confidence: 99%

“…MSCs have been shown to serve as precursors of most types of these cells. 23 Previously, our group reported that endothelial colony-forming cells (ECFCs), which are blood-or vasculature-derived endothelial progenitor cells, characterized by robust proliferative potential, also can form perfused long-lasting blood vessels in vivo. 30 Thus, we hypothesized that we could develop ectopic, extramedullary bones and BM using MSCs and ECFCs.…”

Section: Introductionmentioning

confidence: 99%

“…Sections (5 m) were stained with Alcian blue and analyzed by light microscopy. 23 MSCs before and after the inductions also were harvested for RNA extraction. Real-time RT-PCR was performed on these samples to demine the expression of lipoprotein lipase, collagen type II ␣ 1, and osteocalcin during the differentiation.…”

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confidence: 99%

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Human extramedullary bone marrow in mice: a novel in vivo model of genetically controlled hematopoietic microenvironment

Chen

Jácamo

Shi

et al. 2012

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The interactions between hematopoietic cells and the bone marrow (BM) microenvironment play a critical role in normal and malignant hematopoiesis and drug resistance. These interactions within the BM niche are unique and could be important for developing new therapies. Here, we describe the development of extramedullary bone and bone marrow using human mesenchymal stromal cells and endothelial colony-forming cells implanted subcutaneously into immunodeficient mice. We demonstrate the engraftment of human normal and leukemic cells engraft into the human extramedullary bone marrow. When normal hematopoietic cells are engrafted into the model, only discrete areas of the BM are hypoxic, whereas leukemia engraftment results in widespread severe hypoxia, just as recently reported by us in human leukemias. Importantly, the hematopoietic cell engraftment could be altered by genetical manipulation of the bone marrow microenvironment: Extramedullary bone marrow in which hypoxia-inducible factor 1␣ was knocked down in mesenchymal stromal cells by lentiviral transfer of short hairpin RNA showed significant reduction (50% ؎ 6%; P ‫؍‬ .0006) in human leukemic cell engraftment. These results highlight the potential of a novel in vivo model of human BM microenvironment that can be genetically modified. The model could be useful for the study of leukemia biology and for the development of novel therapeutic modalities aimed at modifying the hematopoietic microenvironment. IntroductionThe relevance of the bone marrow (BM) microenvironment in regulating hematopoietic stem cell (HSC) behavior has only recently been established. [1][2][3][4][5] The maintenance of HSC quiescence and normal hematopoiesis requires complex bidirectional interactions between the BM niche and HSCs. [6][7][8] Moreover, much evidence supports the idea that the BM microenvironment also plays a pivotal role in the initiation and propagation of leukemia. [9][10][11] Leukemic cells have been shown to hijack the homeostatic mechanisms of normal HSCs and take refuge within the BM niche. This mechanism is pivotal during chemotherapy and contributes to disease relapse. 12,13 Although human HSCs can be genetically modified and transplanted into immunodeficient mice, the BM microenvironment is not transplantable. Numerous studies in patients and mice undergoing bone marrow transplantation have failed to demonstrate consistent engraftment of donor BM stroma cells. [14][15][16] A better understanding of the BM niche will not only improve our understanding of HSC self-renewal and hematopoiesis in general but also accelerate the development of new therapeutic modalities and targeted agents for the therapy of hematopoietic malignancies. Although the concept of a BM "niche" was formulated in 1978, it remains largely unidentified owing to technical limitations. 13,[17][18][19] Currently, the xenotransplant NOD/SCID and NOD/SCID/IL-2r␥ null mouse repopulation assays are the most widely used and relevant readout systems for studying human normal and malignant hematopoiesis. H...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Human extramedullary bone marrow in mice: a novel in vivo model of genetically controlled hematopoietic microenvironment

Chen

Jácamo

Shi

et al. 2012

Blood

Self Cite

109

114

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“…Mesenchymal stem cells are multipotent adherent fibroblastic cells capable of differentiating into multiple mesenchymal lineages and other tissue cell types (Seung et al 2005). They can also be greatly expanded ex vivo and are able to migrate to the sites of injury, inflammation, tumors (Chen et al 2008) and are less immunogenic compared to ESCs. They may therefore be considered as alternatives to ESCs in transplantation therapy and reprogramming since their use is not hampered by ethical and regulatory debates as in the case of ESCs.…”

Section: Introductionmentioning

confidence: 99%

Stem cells for reprogramming: could hUMSCs be a better choice?

et al. 2012

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Human umbilical cord mesenchymal stem cells (hUMSC) are primitive multipotent cells capable of differentiating into cells of different lineages. They can be an alternative source of pluripotent cells since they are ethically and regulatory approved, are easily obtained and have low immunogenicity compared to embryonic stem cells which are dogged with numerous controversies. hUMSC can be a great source for cell and transplantation therapy.

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