Mesenchymal stem cells: a perspective from in vitro cultures to in vivo migration and niches

Abstract

Mesenchymal Stromal Progenitor/Stem Cells (MSCs) are a rare population of non-hematopoietic stromal cells, present in the bone marrow and most connective tissues of the body. They are capable of differentiation into mesenchymal tissues such as bone, cartilage, adipose tissue and muscle. In the absence of specific markers, MSCs have been defined following isolation and culture expansion, by their expression of various molecules including CD90, CD105 and CD73 and absence of markers like CD34, CD45, and CD14. MSCs have extensive proliferative ability in culture in an uncommitted state while retaining their multilineage differentiation potential, which make them attractive candidates for biological cell-based tissue repair approaches. However, their identity in their tissues of origin is not clear and the niches in which they reside are not defined. This review addresses the current state of MSC research including the differentiation potency of culture expanded MSCs, expression of chemokines and their receptors in MSCs -both relevant issues for the advocated use of MSCs for tissue repair and their systemic delivery to the affected tissues. It also reviews current knowledge of MSC niches in their native tissues, addressing the relationship with pericytes. Finally, it provides a scientific basis for the requirement of a thorough characterisation of the endogenous MSC niches within their native tissues in vivo. The knowledge of MSC niches will instruct development of innovative therapeutic measures such as producing pharmacological substances that target endogenous MSCs and their niches in order to activate and guide intrinsic repair and to improve disease outcomes.

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

“…Although little is known about the direct interaction between hMSCs and endothelial cells in vivo, [31][32][33][34][35] because of their anatomical position these cells are either in direct cellcell contact or communicate through paracrine signaling within the endochondral template. The results from this study show that the direct interaction between the two cell types has a significant effect on both the migration and the vascularization potential of the endothelial stem cells, as well as the osteogenic potential of hMSCs, even without the use of any osteogenic supplements.…”

“…30 However, to date knowledge about MSC behavior, particularly the interactions between MSCs and endothelial cells within the stem cell niche in vivo, remains largely unknown. [31][32][33][34][35] During endochondral ossification, MSCs, endothelial stem cells, and chondrocytes all reside in proximity within the cartilage template before the invasion by osteoblasts and bone formation. The anatomical location of MSCs and vascular endothelial cells suggests that these two cell types are in direct cell-cell interaction and experience juxtacrine or paracrine signaling within the stem cell niche during endochondral ossification.…”

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

“…Since marker molecule expression can differ in the in vivo and the in vitro situation, and isolated MSCs will probably change the set of surface proteins upon in vitro cultivation, it is questionable if the observed results can be translated in the in vivo situation. Augello et al (2010) hypothesise in their review that the possibility exists that the MSC phenotype varies between in vitro and in vivo mainly because of the removal from their natural environment and the use of artifi cial culture conditions. This hypothesis is based on publications by Jones et al (2002Jones et al ( , 2006) (additional references) that describe MSCs loosing the expression of some surface markers (Stro-1, LNGFR, and HLA-DR) while also acquiring new ones (CD106, CD146) during in vitro cultivation.…”

Neurotherapeutic Effect of Cord Blood Derived CD45+Hematopoietic Cells in Mice after Traumatic Brain Injury

“…2B). The expression of the C-X-C chemokine receptor type 4 (fusin, CXCR4) CD184, 37 and of CD4 (glycoprotein, leu-3, T4) and CD20 (B-lymphocyte antigen), which are T and B lymphocyte markers, 38 was very low, as were the expression levels of MSCs-specific cell-surface antigens 39 such as CD73 (5¢-nucleotidase, 5¢-NT, 5.9%), CD90 (Thy1, 0.3%), and CD105 (Endoglin, END, 4.4%). These results suggest a pan-hematopoietic, nonmesenchymal origin of the sorted CD45 + cells.…”