Abstract
Bone marrow mesenchymal stromal cells (BM MSCs) represent a heterogeneous population of progenitors with potential for generation of skeletal tissues. However the identity of BM MSC subpopulations is poorly defined mainly due to the absence of specific markers allowing in situ localization of those cells and isolation of pure cell types. Here, we aimed at characterization of surface markers in mouse BM MSCs and in their subsets with distinct differentiation potential. Using conditionally immortalized BM MSCs we performed a screening with 176 antibodies and high-throughput flow cytometry, and found 33 markers expressed in MSCs, and among them 3 were novel for MSCs and 13 have not been reported for MSCs from mice. Furthermore, we obtained clonally derived MSC subpopulations and identified bipotential progenitors capable for osteo- and adipogenic differentiation, as well as monopotential osteogenic and adipogenic clones, and thus confirmed heterogeneity of MSCs. We found that expression of CD200 was characteristic for the clones with osteogenic potential, whereas SSEA4 marked adipogenic progenitors lacking osteogenic capacity, and CD140a was expressed in adipogenic cells independently of their efficiency for osteogenesis. We confirmed our observations in cell sorting experiments and further investigated the expression of those markers during the course of differentiation. Thus, our findings provide to our knowledge the most comprehensive characterization of surface antigens expression in mouse BM MSCs to date, and suggest CD200, SSEA4 and CD140a as markers differentially expressed in distinct types of MSC progenitors.
Highlights
Bone marrow stroma is a complex tissue consisting of many cell types, which provide a microenvironment for haematopoiesis and contribute to the maintenance and regeneration of skeletal tissues [1,2,3]
It has been previously noted that cultured human Bone marrow mesenchymal stromal cells (BM mesenchymal stromal cells (MSCs)) are changing their differentiation properties and expression of markers during passaging [27,37,38], which hampers the studies of their properties and makes characterization of BM MSC subtypes complicated
These observations motivated us to perform an extensive characterization of the expression of surface antigens in conditionally immortalized BM MSCs
Summary
Bone marrow stroma is a complex tissue consisting of many cell types, which provide a microenvironment for haematopoiesis and contribute to the maintenance and regeneration of skeletal tissues [1,2,3]. Capacity of stromal cells to differentiate into osteoblasts and chondrocytes makes them an important source for tissue engineering [10,11] and provided success of treatment of patients with osteogenesis imperfecta [12], and immunosuppressive properties have already brought them to application in clinic to suppress graft-versus-host disease, GVHD [13]. These facts underline a need for developing protocols for cell replacement therapies, improving methods for stromal cell isolation and understanding a physiological role of cellular components of bone marrow stroma. Current methods of stromal cell isolation do not allow derivation of a pure population of stem cells and cultured bone marrow stromal cells represent a mixture of their descendants, including progenitors of different types, hereafter referred as mesenchymal stromal cells (MSCs)
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