LNGFR+THY-1+VCAM-1hi+ Cells Reveal Functionally Distinct Subpopulations in Mesenchymal Stem Cells

Mabuchi, Yo; Morikawa, Satoru; Harada, Seiko; Niibe, Kunimichi; Suzuki, Sadafumi; Raffi, François; Houlihan, Diarmaid D.; Akazawa, Chihiro; Okano, Hideyuki; Matsuzaki, Yuji

doi:10.1016/j.stemcr.2013.06.001

Cited by 192 publications

(223 citation statements)

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“…Moreover, uncultured CD271+Thy1+ were detected in the BM of immunocompromised mice upon transplantation and retained their colony formation and trilineage differentiation ability in vitro (Mabuchi et al, 2013). Other combinations such as CD146 and CD105 (Isern et al, 2013) or Integrin aV and PDGF Receptor a (PDGFRa) (also known as CD51 and CD140a, respectively) have been demonstrated to highly enrich for clonogenic cells in the human BM, as demonstrated by sphere formation assay and the ability to support primitive hematopoietic cells in vitro.…”

Section: Reviewmentioning

confidence: 95%

“…Focusing definitions on cell features in vitro has unfortunately not helped resolve features of the cell in vivo and may be misleading, since there is evidence of a marked global gene expression difference depending on whether the cells are freshly isolated or cultured (Churchman et al, 2012;Harichandan et al, 2013). The expression of cell surface molecules such as low-affinity nerve growth factor receptor (LNGFR), also known as CD271, and the melanoma cell adhesion molecule (MCAM), also known as CD146, both of which have been described to label uncultured multipotent MSCs (Mabuchi et al, 2013;Sacchetti et al, 2007;Tormin et al, 2011) are altered when the cells are cultured. In the case of CD271, its expression is lost when cultured in media containing bFGF (Quirici et al, 2002).…”

Section: Historical Backgroundmentioning

confidence: 99%

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Mesenchymal Cell Contributions to the Stem Cell Niche

2015

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Mesenchymal stromal cells (MSCs) are heterogeneous and primitive cells discovered first in the bone marrow (BM). They have putative roles in maintaining tissue homeostasis and are increasingly recognized as components of stem cell niches, which are best defined in the blood. The absence of in vivo MSC markers has limited our ability to track their behavior in vivo and draw comparisons with in vitro observations. Here we review the historical background of BM-MSCs, advances made in their prospective isolation, their developmental origin and contribution to maintaining subsets of hematopoietic cells, and how mesenchymal cells contribute to other stem cell niches.

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Section: Reviewmentioning

confidence: 95%

Section: Historical Backgroundmentioning

confidence: 99%

Mesenchymal Cell Contributions to the Stem Cell Niche

2015

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“…RECs exhibited robust multilineage differentiation and selfrenewal potency, and were therefore considered to be the most primitive and undifferentiated population. 49 Last, in addition to CD146 and THY-1, other markers, such as MSCA-1 and SUSD2, have also been used to isolate subpopulations of MSCs, 50 and furthermore, differences in differentiation potential of single-sorted BMSC-derived CFU-Fs point to a possible hierarchical structure of the primary MSC compartment. 15 Here, our current ongoing single-cell gene expression experiments will hopefully contribute to further clarify this important aspect of primary MSC biology.…”

Section: But Not In the Cd271mentioning

confidence: 99%

Isolation and characterization of primary bone marrow mesenchymal stromal cells

Ghazanfari

Zacharaki

et al. 2016

Annals of the New York Academy of Sciences

145

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Bone marrow (BM) contains a rare population of mesenchymal stromal cells (MSCs), which have been characterized as nonhematopoietic skeletal progenitor cells with central importance for the hematopoietic microenvironment. Classically, MSCs are isolated by plastic adherence and subsequent culture. However, as cultured stromal cells differ from their in vivo progenitors, it is important to identify the phenotype of the primary MSCs to study these cells in more detail. In the past years, several surface markers have been reported to be suitable for effective enrichment of BM-MSCs, and recent data indicate that the putative MSC stem/progenitor cell population in human adult BM is highly enriched in Lin − CD45 − CD271 + CD140a (PDGFR␣) low/− cells. Moreover, surface marker combinations have been described for the isolation of MSCs from murine BM. On the basis of these findings, the role of primary MSCs can now be studied in normal and, importantly, diseased BM. Furthermore, genetically engineered mouse models have been developed as powerful tools to investigate well-defined BM stromal cell populations in vivo. Our discussion aims to provide a concise overview of the current state of the art in BM-MSC isolation in humans and briefly present murine MSC isolation approaches and genetic models.

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“…These cells differentiate into bone and fat on ectopic transplantation in vivo. In 2013, our group reported that the LNGFR and THY-1 double-positive population (i.e., the LT population) have a high CFU-F frequency in the BM [8]. CFU-F can be classified into three different cell groups based on proliferation ability.…”

Section: Prospective Identification and Isolation Of Human Mscsmentioning

confidence: 99%

“…MSCs reside in the non-hematopoietic fraction and can be cultured to form fibroblast-like colonies (colony-forming unit fibroblasts: CFU-Fs) in vitro [4][5][6][7]. MSCs are found in the BM [8,9], umbilical cord blood [10,11], placenta [12,13], dental pulp [14,15], adipose tissue [16][17][18][19], and synovium [20][21][22]. BM-MSCs are thought to function in the maintenance of BM homeostasis, restoration of injured bone, and regulation of differentiation in HSCs [23].…”

Section: Introductionmentioning

confidence: 99%