Origin and Characterization of Multipotential Mesenchymal Stem Cells Derived from Adult Human Trabecular Bone

Abstract

Much of the knowledge regarding the regulatory pathways for adult stem cell self-renewal and differentiation has been obtained from the results of in vitro cultures. However, it is unclear if adult stem cells are controlled in the same way under physiological conditions. We examined this issue with respect to the migration of stem cells to tissue injury and how switch from a migratory state to one of proliferation wherein they participate in development. Building on our previous identification of multipotent stem cells in trabecular bone, we have examined the in vitro behavior of these cells within the bone milieu. We found that cell proliferation is inhibited within the trabecular bone niche as cells migrate out of the trabecular bone prior to proliferation. Additionally, multiple cell types were detected in adult trabecular bone, including osteoblasts, osteoclasts, endothelial cells, and Stro-1-positive mesenchymal stem cells. Furthermore, we demonstrated that Stro-1-positive cells migrated out of their native bone niche to generate multipotential stem and progenitor cells during in vitro culture. We conclude that self-renewal and differentiation of adult stem cells in connective tissues are tightly controlled and separately orchestrated processes. A regulatory network of extrinsic factors and intrinsic signals acts to stimulate the exit of stem cells from their niche so that they can localize to sites of wound healing, where they participate in development after functional differentiation.

miR-29 Modulates Wnt Signaling in Human Osteoblasts through a Positive Feedback Loop

“…For in vitro osteoblastic differentiation, confluent cultures of hFOB cells were maintained in complete medium with the addition of differentiation cocktail as follows: 100 g/l ascorbic acid, 10 Ϫ8 M menadione, 5 mM ␤-glycerol phosphate, and 10 Ϫ7 M 1-25(OH) 2 -vitamin D 3 (all from Sigma) (1). Primary cultures of human osteoblasts were derived from bone chips obtained from healthy individuals undergoing routine orthopedic procedures (37)(38)(39)(40)(41)(42). Isolation of osteoblasts from these de-identified specimens was deemed exempt by the University of Connecticut Health Center Institutional Review Board.…”

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

“…For instance studies have identified bone marrow-derived PDGFR-β + /Sca-1 + /CD11b + pericyte progenitors [102], bone marrow-derived CD45 + /CD11b + progenitors [103], and Sca-1 + /Tie2 + /CD13 + pericyte progenitors that have been associated with tumour development [104]. To our knowledge, there is no information on the osteochondrogenic capacity of these cells and as such their potential roles during HO remains unknown.…”

Porous tantalum stimulates the proliferation and osteogenesis of osteoblasts from elderly female patients

“…These isolated cells had previously been shown to have the potential to become either osteoblasts, adipocytes or chondrocytes and, therefore, have been named ''multipotential mesenchymal stem cells from adult bone''. 15,16 The cells that are grown from human bone also have been shown to be identical in phenotype when differentiated in culture to mesenchymal stem cells obtained from bone marrow aspirates. 17,18 We consider these cells to be multipotential mesenchymal progenitor cells from adult bone but we will call them HOBs representing their differentiated phenotype in the culture conditions employed in this study.…”