Isolation of functionally distinct mesenchymal stem cell subsets using antibodies against CD56, CD271, and mesenchymal stem cell antigen-1

Battula, Venkata Lokesh; Treml, Sabrina; Bareiss, Petra M.; Gieseke, Friederike; Roelofs, Helene; Zwart, Peter de; Müller, Ingo; Schewe, B.; Skutella, Thomas; Fibbe, Willem E.; Kanz, Lothar; Bühring, Hans Jörg

doi:10.3324/haematol.13740

Cited by 317 publications

(303 citation statements)

References 40 publications

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“…W8B2 1 CD56 1 BMSCs can undergo osteoblastic, chondrogenic, myogenic, neuronal, and pancreatic differentiation, while adipocyte differentiation potential is restricted to the W8B2 1 CD56 2 subset of BMSCs [12,13]. Here, we report a population of CRSCs isolated from human adult atrial appendages which are positive for the W8B2 antigen.…”

Section: Introductionmentioning

confidence: 84%

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

et al. 2015

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Cardiac resident stem cells (CRSCs) hold much promise to treat heart disease but this remains a controversial field. Here, we describe a novel population of CRSCs, which are positive for W8B2 antigen and were obtained from adult human atrial appendages. W8B2 1 CRSCs exhibit a spindle-shaped morphology, are clonogenic and capable of self-renewal. W8B2 1 CRSCs show high expression of mesenchymal but not hematopoietic nor endothelial markers. W8B2 1 CRSCs expressed GATA4, HAND2, and TBX5, but not C-KIT, SCA-1, NKX2.5, PDGFRa, ISL1, or WT1. W8B2 1 CRSCs can differentiate into cardiovascular lineages and secrete a range of cytokines implicated in angiogenesis, chemotaxis, inflammation, extracellular matrix remodeling, cell growth, and survival. In vitro, conditioned medium collected from W8B2 1 CRSCs displayed prosurvival, proangiogenic, and promigratory effects on endothelial cells, superior to that of other adult stem cells tested, and additionally promoted survival and proliferation of neonatal rat cardiomyocytes. Intramyocardial transplantation of human W8B2 1 CRSCs into immunocompromised rats 1 week after myocardial infarction markedly improved cardiac function (~40% improvement in ejection fraction) and reduced fibrotic scar tissue 4 weeks after infarction. Hearts treated with W8B2 1 CRSCs showed less adverse remodeling of the left ventricle, a greater number of proliferating cardiomyocytes (Ki67 1 cTnT 1 cells) in the remote region, higher myocardial vascular density, and greater infiltration of CD163 1 cells (a marker for M2 macrophages) into the border zone and scar regions. In summary, W8B2 1 CRSCs are distinct from currently known CRSCs found in human hearts, and as such may be an ideal cell source to repair myocardial damage after infarction. STEM CELLS 2015;33:3100-3113 SIGNIFICANCE STATEMENTWe have isolated a new type of adult stem cell from human heart tissue, which carries markers different from known cardiac resident stem cells. These cells can be rapidly expanded and have powerful regenerative effects when injected into the hearts of rats after heart attack, such that they greatly improve cardiac performance compared with controls that have also suffered heart attack. We showed these cells protect other cells from dying and promote growth of blood vessels, actions which assist cardiac regeneration. Importantly, their protective actions in this regard are superior to those of other adult stem cells that have shown some benefit in clinical trials after heart attack. These new stem cells have great potential for repairing the heart, and could be derived from the individual patients in need, avoiding any problem of immunorejection.

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Section: Introductionmentioning

confidence: 84%

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

et al. 2015

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“…LNGFR is not reactive to red blood cells and hematopoietic progenitor cells, which has made LNGFR one of the more popular markers for the isolation of human MSCs. Some studies have used the LNGFR marker in combination with MSCA-1-positive [51], CD56-positive [52,53], CD140b-positive [54], CD146-positive/negative [55], and SSEA4-positive [56] populations. In addition, high CFU-F frequency is associated with a population double-positive for CD106 (VCAM-1) and Stro-1 antibodies [57].…”

Section: Prospective Identification and Isolation Of Human Mscsmentioning

confidence: 99%

Prospective isolation of resident adult human mesenchymal stem cell population from multiple organs

Mabuchi

Matsuzaki²

2015

Int J Hematol

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“…Surface markers such as stage-specific embryonic Ag-4, STRO-1 and the low-affinity nerve growth factor receptor (CD271) have been employed with the aim to prospectively isolate human MSCs. [9][10][11] Battula et al 12 have recently identified novel MSC subsets with distinct phenotypic and functional properties in human BM by using antibodies directed against the surface Ags CD271, mesenchymal stem cell Ag-1 and CD56. In particular, CD271 has been reported to define a subset of MSCs with immunosuppressive and lymphohematopoietic engraftment-promoting properties in vivo.…”

Section: Msc Surface Markersmentioning

confidence: 99%

“…13 Plateletderived growth factor receptor-b (CD140b) has been also identified as a selective marker for the isolation of clonogenic MSCs; 11 an STRO-4 MoAb has been shown to be specific for mesenchymal precursors cells from human and ovine tissues, being capable of enriching colonyforming fibroblasts when employed for MSC isolation from BM. 14 Despite the identification of these new MSC markers, [8][9][10][11][12][13][14] none of the available reagents has been shown to be singularly capable of identifying the true mesenchymal progenitors. Future research should include the identification of MSC-specific markers, which will hopefully allow one to dissect the developmental hierarchy of MSCs and will facilitate the generation of homogeneous cellular products.…”

Section: Msc Surface Markersmentioning

confidence: 99%

“…6,7 Recently, the identification and prospective isolation of mesenchymal progenitors, both in murine and human adult BM, have been reported, based on the expression of specific markers. [8][9][10][11][12][13][14] Whether culture-expanded MSCs differ from their progenitors in vivo is uncertain, as proliferation on plastic surfaces and culture conditions may induce both phenotypic and functional changes. Anjos-Afonso et al 8 have reported the identification, isolation and characterization of a population of multipotent mesenchymal cells in murine BM, based on the expression of the stage-specific embryonic antigen-1.…”

Section: Msc Surface Markersmentioning

confidence: 99%

See 1 more Smart Citation

Mesenchymal stromal cells: a novel and effective strategy for facilitating engraftment and accelerating hematopoietic recovery after transplantation?

Bernardo

Cometa

Locatelli

2011

Bone Marrow Transplant

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Isolation of functionally distinct mesenchymal stem cell subsets using antibodies against CD56, CD271, and mesenchymal stem cell antigen-1

Cited by 317 publications

References 40 publications

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

Prospective isolation of resident adult human mesenchymal stem cell population from multiple organs

Mesenchymal stromal cells: a novel and effective strategy for facilitating engraftment and accelerating hematopoietic recovery after transplantation?

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