Chondrogenic Potential of Human Adult Mesenchymal Stem Cells Is Independent of Age or Osteoarthritis Etiology

NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
Stem Cells (Impact Factor: 6.52). 12/2007; 25(12):3244-51. DOI: 10.1634/stemcells.2007-0300
Source: PubMed


Osteoarthritis (OA) is a multifactorial disease strongly correlated with history of joint trauma, joint dysplasia, and advanced age. Mesenchymal stem cells (MSCs) are promising cells for biological cartilage regeneration. Conflicting data have been published concerning the availability of MSCs from the iliac crest, depending on age and overall physical fitness. Here, we analyzed whether the availability and chondrogenic differentiation capacity of MSCs isolated from the femoral shaft as an alternative source is age- or OA etiology-dependent. MSCs were isolated from the bone marrow (BM) of 98 patients, categorized into three OA-etiology groups (age-related, joint trauma, joint dysplasia) at the time of total hip replacement. All BM samples were characterized for cell yield, proliferation capacity, and phenotype. Chondrogenic differentiation was studied using micromass culture and analyzed by histology, immunohistochemistry, and quantitative reverse transcriptase-polymerase chain reaction. Significant volumes of viable BM (up to 25 ml) could be harvested from the femoral shaft without observing donor-site morbidity, typically containing >10(7) mononuclear cells per milliliter. No correlation of age or OA etiology with the number of mononuclear cells in BM, MSC yield, or cell size was found. Proliferative capacity and cellular spectrum of the harvested cells were independent of age and cause of OA. From all tested donors, MSCs could be differentiated into the chondrogenic lineage. We conclude that, irrespective of age and OA etiology, sufficient numbers of MSCs can be isolated and that these cells possess an adequate chondrogenic differentiation potential. Therefore, a therapeutic application of MSCs for cartilage regeneration of OA lesions seems feasible. Disclosure of potential conflicts of interest is found at the end of this article.

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Available from: Alwin Scharstuhl, Oct 17, 2014
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    • "Reports about the effect of aging on isolated human MSC proliferation are conflicting. In a number of studies, no significant changes in cultured MSC doubling time or proliferation capacity have been observed in young versus elderly people (Scharstuhl et al. 2007; Suva et al. 2004; Stenderup et al. 2001). In contrast, several research groups suggested that increasing age has a negative impact on MSC growth (Alt et al. 2012; Mareschi et al. 2006; Zaim et al. 2012), cell number and performance (Stolzing et al. 2008). "
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    ABSTRACT: Aging is accompanied by reduced regenerative capacity of all tissues and organs and dysfunction of adult stem cells. Notably, these age-related alterations contribute to distinct pathophysiological characteristics depending on the tissue of origin and function and thus require special attention in a type by type manner. In this paper, we review the current understanding of the mechanisms leading to tissue-specific adult stem cell dysfunction and reduced regenerative capacity with age. A comprehensive investigation of the hematopoietic, the neural, the mesenchymal, and the skeletal stem cells in age-related research highlights that distinct mechanisms are associated with the different types of tissue stem cells. The link between age-related stem cell dysfunction and human pathologies is discussed along with the challenges and the future perspectives in stem cell-based therapies in age-related diseases.
    Full-text · Article · Oct 2013 · Biogerontology
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    • "OA is the most prevalent articular pathology and the most frequent cause of disability. The etiology for OA is unknown but multiple factors such as obesity, age, anatomic abnormalities, history of joint trauma, joint instability, repeated injury, overuse and joint dysplasia are thought to be involved, resulting in severe joint pain, loss of movement, and irreversible functional disability with a marked decrease in quality of life [1,2]. This degenerative process is driven by the activation of the single cell type present in the mature cartilage, chondrocytes [3]. "
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    ABSTRACT: Background Osteoarthritis (OA) is a multifactorial disease characterized by destruction of the articular cartilage due to environmental, mechanical and genetic components. The genetics of OA is complex and is not completely understood. Recent works have demonstrated the importance of microRNAs (miRNAs) in cartilage function. MiRNAs are a class of small noncoding RNAs that regulate gene expression and are involved in different cellular process: apoptosis, proliferation, development, glucose and lipid metabolism. The aim of this study was to identify and characterize the expression profile of miRNAs in normal and OA chondrocytes and to determine their role in the OA. Methods Chondrocytes were moved to aggregate culture and evaluated using histological and qPCR techniques. miRNAs were isolated and analyzed using the Agilent Human miRNA Microarray. Results Of the 723 miRNAs analyzed, 7 miRNAs showed a statistically significant differential expression. Amongst these 7 human miRNAs, 1 was up-regulated in OA chondrocytes (hsa-miR-483-5p) and 6 were up-regulated in normal chondrocytes (hsa-miR-149*, hsa-miR-582-3p, hsa-miR-1227, hsa-miR-634, hsa-miR-576-5p and hsa-miR-641). These profiling results were validated by the detection of some selected miRNAs by qPCR. In silico analyses predicted that key molecular pathways potentially altered by the miRNAs differentially expressed in normal and OA chondrocytes include TGF-beta, Wnt, Erb and mTOR signalling; all of them implicated in the development, maintenance and destruction of articular cartilage. Conclusions We have identified 7 miRNAs differentially expressed in OA and normal chondrocytes. Our potential miRNA target predictions and the signalling cascades altered by the differentially expressed miRNAs supports the potential involvement of the detected miRNAs in OA pathology. Due to the importance of miRNA in mediating the translation of target mRNA into protein, the identification of these miRNAs differentially expressed in normal and OA chondrocyte micropellets could have important diagnostic and therapeutic potential. Further studies are needed to know the function of these miRNAs, including the search of their target mRNA genes, which could lead to the development of novel therapeutic strategies for the OA treatment.
    Full-text · Article · Aug 2012 · BMC Musculoskeletal Disorders
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    • "Phinney et al. found up to 12-fold differences between patients when investigating growth properties of BMSCs from 17 healthy patients aged 19–45 years old; however, this difference showed no correlation with age of donor (P < 0.05) [18]. Both Suva et al. and Scharstuhl et al. extracted BMSCs from the neck and shaft of femur, respectively, at the time of hip arthroplasty [19] [20]. Suva et al. reported variable results for time required to reach the first passage, exponential cell growth, doubling time, and maximal cell amplification, but again none of these variations were found to be due to age-related differences of donors. "
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    ABSTRACT: Adult mesenchymal stem cells (MSCs) are being investigated further for their use in stem cell therapies. However, as they are found in very low numbers in adult tissue, expansion in vitro is required to produce desired MSC numbers for clinical application. The need for effective cell-based therapies is increasing due to a rise in the ageing population, increasing the prevalence of musculoskeletal disorders. This review investigates how factors, age and gender of donor, as well as seeding density can affect MSC expansion. Age and gender of donor have received mixed results from studies, whereas seeding density studies have produced consistent results for numerous MSC sources, favouring lower seeding densities. Further research is required to reduce the risk of infection, loss of cell characterisation in cell culture, and making cell-based therapies more cost effective through creating rapid expansion of MSCs regardless of patient factors.
    Full-text · Article · Jan 2012
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