CD133 Identifies a Human Bone Marrow Stem/Progenitor Cell Sub-population With a Repertoire of Secreted Factors That Protect Against Stroke

Bakondi, Benjamin; Shimada, Issei S.; Perry, Anthony S.; Munoz, James R.; Ylöstalo, Joni; Howard, Ann; Gregory, Carl A.; Spees, Jeffrey L.

doi:10.1038/mt.2009.185

Cited by 79 publications

(115 citation statements)

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“…Extrinsic factors driven by bone marrow microenvironment are reported to regulate the growth of hematopoietic stem cells (67) within supportive osteoblastic and vascular niches (68). Among the soluble factors secreted in BM niches by stem cells (69) and stromal compartment (10), ADM synergizes with stem cell factor and Flt-3 (FMS-like tyrosine kinase-3) ligand to induce the proliferation of primitive human CD34 + CD38 -lin -cells and to promote the expansion of CD34 + progenitors in culture (70). The development of hematopoietic malignancies causes a remodeling of BM microenvironment followed by the alteration of HSC function, leukemia survival, protection of cancer cells from apoptotic stimuli and development of drug-resistant phenotype (67,71).…”

Section: Discussionmentioning

confidence: 99%

Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells

Liddo

Bridi

Gottardi

et al. 2016

International Journal of Oncology

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Abstract. Adrenomedullin (ADM) is a regulatory peptide endowed with multiple biological effects, including the regulation of blood pressure, cell growth and innate host defence. In the present study, we demonstrated that ADM signaling could be involved in the impaired cellular differentiation of myeloid leukemia cells to mature granulocytes or monocytes by modulating RAMPs/CRLR expression, PI3K/Akt cascade and the ERK/MAPK signaling pathway. When exogenously administered to in vitro cultures of HL60 promyelocytic leukemia cells, ADM was shown to exert a strong proliferative effect with minimal upregulation in the expression level of monocyte antigen CD14. Notably, the experimental inhibition of ADM signaling with inhibitor ADM 22-52 promoted a differentiative stimulation towards monocytic and granulocytic lineages. Moreover, based on the expression of CD31 relative to CD38, we hypothesized that an excess of ADM in bone marrow (BM) niche could increase the transendothelial migration of leukemia cells while any inhibitory event of ADM activity could raise cell retention in hyaluronate matrix by upregulating CD38. Taken into consideration the above evidence, we concluded that ADM and ADM 22-52 could differently affect the growth of leukemia cells by autocrine/paracrine mechanisms and may have clinical relevance as biological targets for the intervention of tumor progression.

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Section: Discussionmentioning

confidence: 99%

Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells

Liddo

Bridi

Gottardi

et al. 2016

International Journal of Oncology

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“…Although they may be a source of endothelial or other progenitor cells, they probably act principally through paracrine mechanisms. 1,2 BMDCs are currently being used to treat ischemic conditions in clinical trials. [3][4][5] However, given our rudimentary knowledge of how BMDCs act as agents of vascular growth and tissue repair, it is not surprising that results of clinical trials to date are mixed.…”

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confidence: 99%

Lin− Cells Mediate Tissue Repair by Regulating MCP-1/CCL-2

Schatteman

Awad

Nau

et al. 2010

The American Journal of Pathology

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Exogenous bone marrow-derived cells (BMDCs) are promising therapeutic agents for the treatment of tissue ischemia and traumatic injury. However , until we identify the molecular mechanisms that underlie their actions , there can be no rational basis for the design of therapeutic strategies using BMDCs. The pro-healing effects of BMDCs are apparent very shortly after treatment , which suggests that they may exert their effects by the modulation of acute inflammation. We investigated this hypothesis by taking advantage of the fact that BMDCs from healthy , young, but not obese , diabetic mice stimulate vascular growth. By comparing both in vitro secretion and in vivo local induction of acute phase inflammatory cytokines by these cells , we identified monocyte chemoattractant factor 1 and tumor necrosis factor ␣ as potential mediators of BMDC-induced tissue repair. In vivo analysis of BMDC-treated ischemic limbs and cutaneous wounds revealed that the production of monocyte chemoattractant factor 1 by exogenous and endogenous BMDCs is essential for BMDC-mediated vascular growth and tissue healing , while the inability of BMDCs to produce tumor necrosis factor ␣ appears to play a lesser but still meaningful role. Thus, measurements of the secretion of cytokines by BMDCs may allow us to identify a priori individuals who would or would not be good candidates for BMDC-based therapies.

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“…Different from previous methods [13,15,18,21], this method did not require colonies selection or specific markers for cell sorting; rather, it utilized the different particle-engulfing abilities of different BMSC subpopulations for cell separation. At first, this method was designed to remove the abundant contaminating macrophages in the primary mouse BMSCs due to their high particle-engulfing abilities.…”

Section: Discussionmentioning

confidence: 99%

Efficient Isolation of Bone Marrow Adipocyte Progenitors by Silica Microbeads Incubation

Liu²,

Cao³

2013

Stem Cells and Development

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Excessive bone marrow adipocytes (BMAs) formation is tightly associated with development of osteoporosis. Considering the high heterogeneity of bone marrow stromal cells (BMSCs), identification of bone marrow adipocyte progenitors (BMAPs) within heterogeneous BMSCs may provide better cellular models for research regarding osteoporosis development and therapy. However, currently there is no efficient method or specific surface makers that are available for BMAPs isolation. In the current study, we developed a novel BMAPs isolation method based on silica microbeads incubation and subsequent centrifugation in ficoll-paque. The ''Sca-1+ '' subpopulation selected by this method exhibited significantly stronger adipogenic potential than nonselected BMSCs in vitro and could homogeneously differentiate into mature adipocytes within 4 days. Moreover, these cells also highly expressed a series of adipogenesis-related genes even before differentiation. After long-term culture, however, BMAPs would gradually lose high adipogenic ability, but sorting CD105 + cells from BMAPs in later passages was able to retrieve the highly adipogenic subpopulation. In conclusion, this study demonstrated that BMAPs subpopulation could be effectively isolated from heterogeneous BMSCs by a special silica microbeads incubation method and re-enriched by sorting CD105 + cells. These findings offer convenient and repeatable approaches to obtain pure BMAPs for research regarding pathogenic mechanisms and therapeutics development of osteoporosis.

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CD133 Identifies a Human Bone Marrow Stem/Progenitor Cell Sub-population With a Repertoire of Secreted Factors That Protect Against Stroke

Cited by 79 publications

References 50 publications

Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells

Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells

Lin− Cells Mediate Tissue Repair by Regulating MCP-1/CCL-2

Efficient Isolation of Bone Marrow Adipocyte Progenitors by Silica Microbeads Incubation

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