Myogenic Properties of Human Mesenchymal Stem Cells Derived from Three Different Sources

Abstract

Mesenchymal stem cells (MSCs) of mammals have been isolated from many tissues and are characterized by their aptitude to differentiate into bone, cartilage, and fat. Differentiation into cells of other lineages like skeletal muscle, tendon/ligament, nervous tissue, and epithelium has been attained with MSCs derived from some tissues. Whether such abilities are shared by MSCs of all tissues is unknown. We therefore compared for three human donors the myogenic properties of MSCs from adipose tissue (AT), bone marrow (BM), and synovial membrane (SM). Our data show that human MSCs derived from the three tissues differ in phenotype, proliferation capacity, and differentiation potential. The division rate of AT-derived MSCs (ATMSCs) was distinctly higher than that of MSCs from the other two tissue sources. In addition, clear donorspecific differences in the long-term maintenance of MSC proliferation ability were observed. Although similar in their in vitro fusogenic capacity with murine myoblasts, MSCs of the three sources contributed to a different extent to skeletal muscle regeneration in vivo. Transplanting human AT-, BM-, or SM-MSCs previously transduced with a lentiviral vector encoding β-galactosidase into cardiotoxin-damaged tibialis anterior muscles (TAMs) of immunodeficient mice revealed that at 30 days after treatment the frequency of hybrid myofibers was highest in the TAMs treated with AT-MSCs. Our finding of human-specific β-spectrin and dystrophin in hybrid myofibers containing human nuclei argues for myogenic programming of MSCs in regenerating murine skeletal muscle. For the further development of MSC-based treatments of myopathies, AT-MSCs appear to be the best choice in view of their efficient contribution to myoregeneration, their high ex vivo expansion potential, and because their harvesting is less demanding than that of BM-or SM-MSCs.

Synovia-Derived Mesenchymal Stem Cell Application in Musculoskeletal Injuries: A Review

“…MSCs from different sources present unlike characteristics, such as phenotype, proliferation capacity, and differentiation ability [29,38], thus affecting the cell biological properties and therapeutic potential [4]. These intrinsic differences are influenced by the tissue of origin environmental factors [12,29].…”

“…Regenerative medicine approaches regarding stem cell therapies have been developed in the past decades as a promising strategy, focusing primarily on immune/anti-inflammatory modulation [15] and cancer treatment [29]. Furthermore, their potential has been employed in cartilage [30] and skeletal muscle repair [1], the latter in a more immature state of development.…”

“…The parallel expression or exclusion of several cell surface markers, associated with other ISCT criteria, is a frequent approach to MSC identification [41]. They share nonhematopoietic cell surface markers, such as CD29, CD44, CD73, CD90, and CD105 and human lymphocyte antigen (HLA) [29]; CD9, CD44, CD54, CD90, CD166 [41]; and CD44, CD79, CD90, CD105 [39]. They are usually negative for hematopoietic markers, such as CD34 e CD45 [39].…”

“…They are characterized by an extensive proliferation ability in culture and have the potential to differentiate in vitro into different lineages [5,32,33,36], including adipogenic, chondrogenic, osteogenic [6,29,31,35], myogenic [6,31,35,37], and neurogenic [6,37].…”

“…MSCs were first harvested from the bone marrow by Friedenstein in 1976 [29,31,32], but now their presence is well established in virtually all postnatal tissues [5,[31][32][33][34], being involved in the tissue growth and homeostasis [31]. They have since been isolated from different adult tissues [30-32, 35, 36], such as fat, bone marrow, bone, cartilage [6], periosteum [32], nervous tissues, tendon, ligament, epithelium, SM, lung, peripheral blood, skeletal muscle, and nonadult tissues, such as amniotic fluid, placenta, and umbilical cord blood and stroma [29].…”