Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy

Abstract

A considerable amount of retrospective data is available that describes putative mesenchymal stem cells (MSCs). However, there is still very little knowledge available that documents the properties of a MSC in its native environment. Although the precise identity of MSCs remains a challenge, further understanding of their biological properties will be greatly advanced by analyzing the mechanisms that govern their self-renewal and differentiation potential. This review begins with the current state of knowledge on the biology of MSCs, specifically with respect to their existence in the adult organism and postulation of their biological niche. While MSCs are considered suitable candidates for cell-based strategies owing to their intrinsic capacity to self-renew and differentiate, there is currently little information available regarding the molecular mechanisms that govern their stem cell potential. We propose here a model for the regulation of MSC differentiation, and recent findings regarding the regulation of MSC differentiation are discussed. Current research efforts focused on elucidating the mechanisms regulating MSC differentiation should facilitate the design of optimal in vitro culture conditions to enhance their clinical utility cell and gene therapy.

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

“…Despite in vivo characterization, it is believed that MSCs play an important role in human development, postnatal growth, repair, regeneration, and homeostasis (32). Findings of the present in vitro study suggest that the different in vivo functions of MSCs may be dependent on their resident location.…”

“…These diverse findings on MSC phenotype indicate a lack of consensus concerning the value of STRO-1 as a single marker (32).…”

The role of “cell therapy” in osteonecrosis of the femoral head

“…Current research has focused on clarifying the molecular mechanisms involved in the pathogenesis of ONFH (Gangji and Hauzeur 2009, Kasten et al 2008, Lee et al 2009). Particular attention has been paid to multipotent mesenchymal stem cells (MSCs) and their ability to maintain mitotic multiplication while being capable of differentiating into various cellular types, such as osteoblasts, osteocytes, chondrocytes, and adipocytes (Baksh et al 2004). Experimentally, MSCs have been shown to enhance tissue regeneration when transplanted in areas of necrotic bone (Yan et al 2009).…”

Site-specific gene modification by oligodeoxynucleotides in mouse bone marrow-derived mesenchymal stem cells

“…Based on the current data, MSCs are thought to be negative for hematopoietic surface markers such as CD34, CD45, CD14, CD31, CD133 and positive for CD105, CD166, CD54, CD55, CD13 and CD44 (11)(12)(13)(14)(15)(16)(17)(18). 1,3,42 Despite the fact that no perspective markers exclusively defining MSC are currently available, there is also general agreement that MSCs lack typical hematopoietic antigens, such as CD45, CD34 and CD14.…”

“…Bone marrow contains mesenchymal progenitor cells, called mesenchymal stem cells (MSCs) that have the capacity to differentiate into a variety of unique mesenchymal tissues including bone, cartilage, muscle, fat, tendon, marrow stroma and other connective tissues. [1][2][3][4][5] The multipotential of MSCs, their relatively easy isolation, culture and ex vivo expansive potential have attracted considerable attention in efforts to develop cell and gene therapies and have made these cells an attractive therapeutic tool in a wide range of clinical applications. 6 During the past decade many different viral vectors including retrovirus, 7 adenovirus, [8][9][10][11][12][13] lentivirus [13][14][15][16] and adeno-associated virus 13,[17][18][19][20] have been utilized to deliver genes to or modify genes in MSCs.…”