Superior Osteogenic Capacity for Bone Tissue Engineering of Fetal Compared with Perinatal and Adult Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) from human adult bone marrow (haMSCs) represent a promising source for bone tissue engineering. However, their low frequencies and limited proliferation restrict their clinical utility. Alternative postnatal, perinatal, and fetal sources of MSCs appear to have different osteogenic capacities, but have not been systematically compared with haMSCs. We investigated the proliferative and osteogenic potential of MSCs from human fetal bone marrow (hfMSCs), human umbilical cord (hUCMSCs), and human adult adipose tissue (hATMSCs), and haMSCs, both in monolayer cultures and after loading into three-dimensional polycaprolactone-tricalcium-phosphate scaffolds.Although all MSCs had comparable immunophenotypes, only hfMSCs and hUCMSCs were positive for the embryonic pluripotency markers Oct-4 and Nanog. hfMSCs expressed the lowest HLA-I level (55% versus 95%-99%) and the highest Stro-1 level (51% versus 10%-27%), and had the greatest colony-forming unit-fibroblast capacity (1.6؋-2.0؋; p < .01) and fastest doubling time (32 versus 54 -111 hours; p < .01). hfMSCs had the greatest osteogenic capacity, as assessed by von-Kossa staining, alkaline phosphatase activity (5.1؋-12.4؋; p < .01), calcium deposition (1.6؋-2.7؋ in monolayer and 1.6؋-5.0؋ in scaffold culture; p < .01), calcium visualized on micro-computed tomography (3.9؋17.6؋; p < .01) and scanning electron microscopy, and osteogenic gene induction. Two months after implantation of cellular scaffolds in immunodeficient mice, hfMSCs resulted in the most robust mineralization (1.8؋-13.3؋; p < .01).The ontological and anatomical origins of MSCs have profound influences on the proliferative and osteogenic capacity of MSCs. hfMSCs had the most proliferative and osteogenic capacity of the MSC sources, as well as being the least immunogenic, suggesting they are superior candidates for bone tissue engineering. STEM CELLS 2009;27: 126 -137 Disclosure of potential conflicts of interest is found at the end of this article.

Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression

“…Our data might suggest that BM-MSCs have a weaker response overall and in particular for the radioprotection of vascular EC. Affirmative, earlier reports already suggested that BM-MSCs were less effective for MSC therapy compared to other stem cell sources, for example, compared to adipose tissue-derived or fetal MSCs (64,66,86).…”

Human Periosteum Is a Source of Cells for Orthopaedic Tissue Engineering: A Pilot Study

“…Although this needs to be confirmed in future studies, it may be an example of the role that ''community effects'' or cell-cell interactions/ secreted factors have on the maintenance and control of periosteal progenitor cell populations [2,3]. As well as the colony-forming capacity of Stro-1 + cells, they have been linked with enhanced osteogenicity in vitro [16,48] and cementogenesis in teeth [34]. These observations are confirmed here by a decrease in overall culture when Stro-1 + cells were removed from the general cell population.…”

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

“…However, the majority of studies used ECs [19][20][21][22][23] rather than ECFC. In this project, well-characterized UCB-ECFC were cocultured with hfMSC [7] chosen primarily for their ability to undergo a well-defined osteogenic differentiation pathway [7,24,25] and superiority in osteogenic differentiation over adult counterparts [7,25] for bone tissue engineering applications. We unexpectedly found a twofold enhancement in the osteogenic differentiation of hfMSC when cocultured with UCB-ECFC, and showed that this effect was at least in part through paracrine signaling involving secreted members of the TGF-b superfamily.…”

“…Isolation, Culture, and Characterization of hfMSC and ECFC hfMSC were isolated from bone marrow as previously described [7]. Briefly, single-cell suspensions were prepared by flushing the bone marrow cells from femurs using a 22-gauge needle, passed through a 70 lm cell strainer (BD Biosciences, San Jose, California, http://www.bdbiosciences.com/home.jsp), and plated on 10-cm diameter plates (NUNC, Thermo Scientific, Rochester, NY, www.nuncbrand.com/us/page.aspx?ID=1238) at 10 6 cells per milliliter.…”

“…S2). They had a colony-forming unit-fibroblast (CFU-F) efficiency of 75.1% 6 5.0% and differentiated into osteoblasts, adipocytes, and chondrocytes in permissive media [7,12].…”