Mesenchymal stem cells in rabbit meniscus and bone marrow exhibit a similar feature but a heterogeneous multi-differentiation potential: superiority of meniscus as a cell source for meniscus repair

Abstract

BackgroundThe restoration of damaged meniscus has always been a challenge due to its limited healing capacity. Recently, bone marrow-derived mesenchymal stem cells (BMSCs) provide a promising alternative to repair meniscal defects. However, BMSCs are not ideal chondroprogenitor cells for meniscus repair because they have a high propensity for cartilage hypertrophy and bone formation. Our hypothesis is that mesenchymal stem cells (MSCs) reside in meniscus maintain specific traits distinct from others which may be more conducive to meniscus regeneration.MethodsMSCs were isolated from bone marrow and menisci of the rabbits. The similarities and differences between BMSCs and MMSCs were investigated in vitro by a cell culture model, ex vivo by a rabbit meniscus defect model and in vivo by a nude rat implantation model using histochemistry, immunocytochemistry, qRT-PCR and western blotting.ResultsOur data showed that two types of MSCs have universal stem cell characteristics including clonogenicity, multi-potency and self-renewal capacity. They both express stem cell markers including SSEA-4, Nanog, nucleostemin, strol-1, CD44 and CD90.However, MMSCs differed from BMSCs. MMSC colonies were much smaller and grew more slowly than BMSC colonies. Moreover, fewer MMSCs expressed CD34 than BMSCs. Finally, MMSCs always appeared a pronounced tendency to chondrogenic differentiation while BMSCs exhibited significantly greater osteogenic potential, whatever in vitro and in vivo.ConclusionsThis study shows the similarities and differences between MMSCs and BMSCs for the first time. MMSCs are a promising source of mesenchymal stem cells in repairing meniscus defect.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0511-8) contains supplementary material, which is available to authorized users.

Stem Cell-Based Therapies for Osteoarthritis: From Pre-Clinical to Clinical Applications

“…The histological outcomes confirmed formation of the hyaline cartilage-like tissue expressing collagen type II [55,56,58,59] as well as collagen type I [55,56,58]. Note that, the latter is a marker of fibrocartilaginous tissue.…”

Stem cell delivery in tissue-specific hydrogel enabled meniscal repair in an orthotopic rat model

“…Exogenous stem cells can in turn stimulate endogenous repair cells to produce new tissue. Previous studies have found that the meniscus itself contains a subpopulation of multipotential cells [23,30,36,64], which can be utilized to regenerate tissue. Moreover, the combination of MSCs with native meniscal cells is known to prevent MSC hypertrophy [65,66].…”

“…Prior studies have reported promising results in meniscal regeneration utilizing meniscus ECM preparations in allograft [16,20,70], hydrogel [43,44], and soluble [46] forms; MSCs derived from the bone marrow [71–73], synovium [29], and meniscus [23,31]; and evaluation in animal models ranging from subcutaneous implantation [43,45] to intra-articular injections in rats [29,31,72] up to primates [74]; but none have studied the combination of MSCs and meniscus ECM hydrogel at their relevant site of action. We demonstrate the use of decellularized bovine meniscus hydrogel for intra-articular delivery of human mesenchymal stem cells in an orthotopic nude rat model of meniscal injury.…”

“…Mesenchymal stem cells (MSCs) were selected for our study as they have been widely studied in musculoskeletal diseases [21–23], with previous clinical reports on their use in meniscal repair and OA treatment [24,25]. To improve repair outcomes, hMSCs need to differentiate and grow new tissue, and to produce trophic factors for tissue remodeling and regeneration.…”

Characterization and Comparison of Postnatal Rat Meniscus Stem Cells at Different Developmental Stages

“…These cells possess self‐renewal capacity and multi‐differentiation potential and have immunosuppressive properties . The inherent capacity for expression of type II collagen by MeSCs is greater than that of BMSCs and SMSCs . Several studies have used MeSCs for meniscus tissue engineering, which has shown much potential for meniscus regeneration, thereby delaying or reducing the progression of OA induced by meniscectomy .…”