Two Distinct Stem Cell Lineages in Murine Bone Marrow

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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“…With regard to the phenotype of primary MSCs in murine BM, Koide et al 51 reported that the marker combination PDGFR␣ + Sca-1…”

Section: Prospective Isolation Of Murine Bm-mscs Based On Surface Marmentioning

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

147

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“…However, given the heterogeneity of the bone marrow and the multiple molecular markers identified so far, it is unclear whether bone marrow actually contains an endogenous group of skeletal stem cells that can be recruited systemically during bone repair to form cartilage and/or bone. [41][42][43] The difficulty comes from the small percentage of MSCs within the bone marrow and their close association with cells from the hematopoietic lineage. 44 Further in vivo analyses are required to better understand BMSCs' normal physiological functions.…”

Section: Systemic Recruitment Of Cells During Bone Repairmentioning

confidence: 99%

Cell Sources for Bone Tissue Engineering: Insights from Basic Science

Colnot

2011

Tissue Engineering Part B: Reviews

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One of the goals of bone tissue engineering is to design delivery methods for skeletal stem/progenitor cells to repair or replace bone. Although the materials used to retain cells play a central role in the quality of the constructs, the source of cells is key for bone regeneration. Bone marrow is the most common cell source, but other tissues are now being explored, such as the periosteum, fat, muscle, cord blood, and embryonic or induced pluripotent stem cells. The therapeutic effect of exogenous stem/progenitor cells is accepted, yet their contribution to bone repair is not well defined. The in vitro osteo- and/or chondrogenic potential of these skeletal progenitors do not necessarily predict their differentiation potential in vivo and their function may be affected by their ability to home correctly to bone. This review provides an overview of animal models used to test the efficacy of cell-based approaches. We examine the mechanisms of endogenous cell recruitment during bone repair and compare the role of local versus systemic cell recruitment. We discuss how the normal repair process can help define efficacious cell sources for bone tissue engineering and improve their methods of delivery.

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“…Lastly, it has been shown that a subset of CD45(þ) Lin(À) bone marrow cells was able to differentiate in vitro into a variety of cell types, including endothelial cells, osteoblasts, muscle cells, and neural cells [Rogers et al, 2007]. Interestingly, others have failed to confirm that MSCs and HSCs may share a common lineage [Koide et al, 2007]. Further investigations are needed to clarify the discrepancies among the different studies, which nonetheless do raise questions about either the reliability of CD45 as an exclusive hematopoietic cell marker or, rather, the existence of a clear boundary between HSCs and MSCs.…”

Section: Origin Of Bone Marrow Mscs and Char-acterization Of Their Nichementioning

confidence: 99%

Bone marrow mesenchymal stem cells

Ohishi

Schipani

2009

J of Cellular Biochemistry

103

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Following the identification of bone marrow multipotent cells that could adhere to plastic and differentiate along numerous mesenchymal lineages in vitro, a considerable effort has been invested in characterizing and expanding these cells, which are now called "mesenchymal stem cells" (MSCs), in vitro. Over the years, numerous lines of evidence have been provided in support of their plasticity, their extraordinary immunomodulatory properties, their potential use for tissue engineering purposes, as well as their ability to be recruited to sites of injury, where they might contribute a "natural in vivo system for tissue repair." Moreover, some studies have attempted the characterization of their cell-surface specific antigens and of their anatomical location in vivo. Lastly, it has been shown that similar cells could be also isolated from organs other than the bone marrow. Despite this impressive body of investigations, numerous questions related to the developmental origin of these cells, their proposed pluripotency, and their role in bone modeling and remodeling and tissue repair in vivo are still largely unanswered. In addition, both a systematic phenotypic in vivo characterization of the MSC population and the development of a reproducible and faithful in vivo assay that would test the ability of MSCs to self-renew, proliferate, and differentiate in vivo are just beginning. This brief review summarizes the current knowledge in the field of study of MSCs and the outstanding questions.

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Two Distinct Stem Cell Lineages in Murine Bone Marrow

Cited by 68 publications

References 53 publications

Isolation and characterization of primary bone marrow mesenchymal stromal cells

Isolation and characterization of primary bone marrow mesenchymal stromal cells

Cell Sources for Bone Tissue Engineering: Insights from Basic Science

Bone marrow mesenchymal stem cells

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