Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue

Abstract

Mesenchymal stem cells (MSCs) represent a promising tool for new clinical concepts in supporting cellular therapy. Bone marrow (BM) was the first source reported to contain MSCs. However, for clinical use, BM may be detrimental due to the highly invasive donation procedure and the decline in MSC number and differentiation potential with increasing age. More recently, umbilical cord blood (UCB), attainable by a less invasive method, was introduced as an alternative source for MSCs. Another promising source is adipose tissue (AT). We compared MSCs derived from these sources regarding morphology, the success rate of isolating MSCs, colony frequency, expansion potential, multiple differentiation capacity, and immune phenotype. No significant differences concerning the morphology and immune phenotype of the MSCs derived from these sources were obvious. Differences could be observed concerning the success rate of isolating MSCs, which was 100% for BM and AT, but only 63% for UCB. The colony frequency was lowest in UCB, whereas it was highest in AT. However, UCB-MSCs could be cultured longest and showed the highest proliferation capacity, whereas BM-MSCs possessed the shortest culture period and the lowest proliferation capacity. Most strikingly, UCB-MSCs showed no adipogenic differentiation capacity, in contrast to BM-and AT-MSCs. Both UCB and AT are attractive alternatives to BM in isolating MSC: AT as it contains MSCs at the highest frequency and UCB as it seems to be expandable to higher numbers. STEM CELLS 2006;24: 1294 -1301

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

“…Allogeneic transplantation of MSCs may have a logistic advantage because they are ready to use “off the shelf” in the clinical setting. Moreover, UCB‐derived MSCs exhibit several advantages over adult tissue‐derived MSCs including lower immunogenicity 16, 36 and higher proliferation capacity, paracrine potency, and therapeutic efficacy both in vitro 17, 18 and in vivo 37. These MSCs show karyotypic stability and no senescence up to the 11th passage.…”

“…Human umbilical cord blood (UCB) is a promising source of MSCs. In comparison to adult tissue‐derived MSCs, its advantages include easier extraction, lower immunogenicity 16, higher in vitro proliferation capacity 17, 18, and better in vivo therapeutic efficacy 19. Recently, we have shown that xenotransplantation of human UCB‐derived MSCs significantly attenuates brain injury and the progress of PHH after severe IVH in immunocompetent newborn rats 15, 20, 21.…”

Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies?

“…In 1961, Hayflick and Moorhead discovered that in vitro, human skin fibroblasts undergo only a limited number of population doublings (termed Hayflick limit), and that this number decreased with increasing donor age (Hayflick and Moorhead, 1961). Similar to other human diploid cells, MSC exhibit replicative senescence in vitro, as demonstrated by a number of investigators (Fehrer et al, 2007;Kern et al, 2006;Stenderup et al, 2003;Stenderup et al, 2004;Stolzing et al, 2008). The in vitro senescent phenotype includes the following characteristic features: (i) irreversible arrest of cell division (in contrast to quiescence, where this lock is reversible), (ii) resistance to apoptotic death, and (iii) the excretion of molecules normally secreted during wound repair and infection, such as inflammatory cytokines, proteases and growth factors, the latter having detrimental consequences for the surrounding tissue (Campisi, 2001).…”

“…The in vitro senescent phenotype includes the following characteristic features: (i) irreversible arrest of cell division (in contrast to quiescence, where this lock is reversible), (ii) resistance to apoptotic death, and (iii) the excretion of molecules normally secreted during wound repair and infection, such as inflammatory cytokines, proteases and growth factors, the latter having detrimental consequences for the surrounding tissue (Campisi, 2001). Some, but not all of these characteristics have also been described for MSC cultures (Fehrer et al, 2007;Kern et al, 2006;Stenderup et al, 2003;Stenderup et al, 2004;Stolzing et al, 2008)…”

Cellules souches mésenchymateuses

“…Si, en ce domaine, il n'existe pas d'exigence de la part des autorités de régula-tion, il faudra se pencher sur ce problème, surtout en cas d'utilisation de donneurs dits uniques. De nombreux tissus sont des sources potentielles de CSM : la moelle osseuse, le tissu adipeux et le sang de cordon sont les plus utilisés actuellement [6]. La moelle osseuse et le tissu adipeux sont d'accès facile, et les CSM -dont la quantité est estimée par le nombre de CFU-F mesuré en culture -sont plus abondantes dans le tissu adipeux que dans la moelle osseuse [35] (➜).…”