Bone Tissue-Engineered Implants Using Human Bone Marrow Stromal Cells: Effect of Culture Conditions and Donor Age

Abstract

At present, it is well known that populations of human bone marrow stromal cells (HBMSCs) can differentiate into osteoblasts and produce bone. However, the amount of cells with osteogenic potential that is ultimately obtained will still be dependent on both patient physiological status and culture system. In addition, to use a cell therapy approach in orthopedics, large cell numbers will be required and, as a result, knowledge of the factors affecting the growth kinetics of these cells is needed. In the present study we investigated the effect of dexamethasone stimulation on the in vivo osteogenic potential of HBMSCs. After a proliferation step, the cells were seeded and cultured on porous calcium phosphate scaffolds for 1 week, and then subcutaneously implanted in nude mice for 6 weeks, in order to evaluate their in vivo bone-forming ability. Furthermore, the effect of donor age on the proliferation rate of the cultures and their ability to induce in vivo bone formation was studied. In 67% of the assayed patients (8 of 12), the presence of dexamethasone in culture was not required to obtain in vivo bone tissue formation. However, in cultures without bone-forming ability or with a low degree of osteogenesis, dexamethasone increased the bone-forming capacity of the cells. During cellular proliferation, a significant age-related decrease was observed in the growth rate of cells from donors older than 50 years as compared with younger donors. With regard to the effect of donor age on in vivo bone formation, HBMSCs from several donors in all age groups proved to possess in vivo osteogenic potential, indicating that the use of cell therapy in the repair of bone defects can be applicable irrespective of patient age. However, the increase in donor age significantly decreased the frequency of cases in which bone formation was observed.

Isolation, characterization and differentiation of mesenchymal stem cells from amniotic fluid, umbilical cord blood and Wharton's jelly in the horse

“…A negative correlation between donor age, number and proliferative capacity of MSCs isolated from young and old donors has been demonstrated by several authors (Martin et al 1970, Schneider & Mitsui 1976, Majors et al 1997, D'Ippolito et al 1999, Stenderup et al 2003, Mareschi et al 2006, but widely different results have been obtained with regard to MSC antigen expression. Recently, Stolzing et al (2008) confirmed those already demonstrated in previous studies (D 'Ippolito et al 1999, Mendes et al 2002, Chen et al 2005, Zhang et al 2005, Zheng et al 2007, Kretlow et al 2008, observing a significant age-related change in membrane markers expression levels, an alkaline phosphatase activity, chondrogenic and myogenic differentiation potency decline with donor age in contrast with adipogenic differentiation. However, these data are in contrast with those reported by other research groups (Bergman et al 1996, Stenderup et al 2001, Bellows et al 2003, which showed no age-related differences in differentiation potency.…”

Human Embryonic Stem Cell-Derived Mesenchymal Stem Cell Seeding on Calcium Phosphate Cement-Chitosan-RGD Scaffold for Bone Repair

“…However, the use of hBMSCs has limitations. First, the self-renewal and proliferative ability of hBMSCs decreases due to aging [17][18][19] and diseases, such as osteoporosis and arthritis. 20,21 Second, the heterogeneity of adult stem cells from bone marrow indicates that only a very small proportion of cells can be considered stem cells and can differentiate into the osteogenic lineage.…”

Mechanobiology of Fracture Healing: Basic Principles and Applications in Orthodontics and Orthopaedics

“…Three different cases were considered: young (up to 20 years old), adult (about 55 years old) and elder (more than 70 years old) patients. Based on the histological analyses conducted by Chen et al, (Chen et al, 2005), Baxter et al, (Baxter et al, 2004), Mendes et al (Mendes et al, 2002), and Park et al (Park et al, 2005), the diffusion coefficient D was hypothesized to be a function of the patient's age. Let t elder , t adult and t young be the time periods required by MSCs for recovering completely the bone callus domain respectively for the elder, adult and young patients.…”