A study to identify and characterize the stem/progenitor cell in rabbit meniscus

Abstract

The repair of meniscus in the avascular zone remains a great challenge, largely owing to their limited healing capacity. Stem cells based tissue engineering provides a promising treatment option for damaged meniscus because of their multiple differentiation potential. We hypothesized that meniscusderived stromal cells (MMSCs) may be present in meniscal tissue, and if their pluripotency and character can be established, they may play a role in meniscal healing. To test our hypothesis, we isolated MMSCs, bone marrow-derived stromal cells (BMSCs) and fibrochondrocytes from rabbits. In order to avoid bone marrow mesenchymal stromal cell contamination, the parameniscal tissues and vascular zone of meniscus were removed. The characters of these three types of cells were identified by evaluating morphology, colony formation, proliferation, immunocytochemistry and multi-differentiation. Moreover, a wound in the center of rabbit meniscus was created and used to analyze the effect of BMSCs and MMSCs on wounded meniscus healing. BMSCs & MMSCs expressed the stem cell markers SSEA-4, Nanog, nucleostemin and STRO-1, while fibrochondrocytes expressed none of these markers. Morphologically, MMSCs displayed smaller cell bodies and larger nuclei than ordinary fibrochondrocytes. Moreover, it was certified that MMSCs and BMSCs were all able to differentiate into adipocytes, osteocytes, and chondrocytes in vitro. However, more cartilage formation was found in wounded meniscus filled with MMSCs than that filled with BMSCs. We showed that rabbit menisci harbor the unique cell population MMSCs that has universal stem cell characteristics and posses a tendency to differentiate into chondrocytes. Future research should investigate the mechanobiology of MMSCs and explore the possibility of using MMSCs to more effectively repair or regenerate injured meniscus.

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

“…). These results were consistent with previous studies . Furthermore, MeSCs‐7d‐in the injection group enhanced more neo‐tissue formation and suppressed OA progression better, as compared to the MeSCs‐7d‐mix injection group (Figs.…”

“…In previous studies, our team have reported that intra‐articular injection of MeSCs enhances the regeneration of the injured meniscus and delay or reduce the progression of OA induced by meniscectomy . Huang et al also reported that MeSCs may play a greater role in repair or regeneration of meniscus. Currently, injection of MeSCs has not been used clinically.…”

Characteristics of meniscus progenitor cells migrated from injured meniscus

“…Endogenous MPCs have similar characteristics with in vitro expanded MPCs by collagenase digestion . In spite of their outstanding proliferation, the population of progenitors harvested by collagen‐digestion were extremely low with less than 0.1%.…”

“…However, there are also drawbacks to the MSC‐based approach: MSC isolation requires an invasive biopsy, and the cell culture step required to expand populations can lead to deleterious changes in phenotype . Like MSCs, progenitor cells present in the meniscus are self‐renewing and multipotent, suggesting there is potential for meniscal repair without the need for MSC harvest and implantation …”

Novel Approaches in Meniscal Repair Utilizing Mesenchymal Stem Cells, New Generation Bioscaffolds and Biological Adhesives as Cell Delivery Vehicles

“…Direct intra-synovial injections of MSCs have also been employed and meniscal regeneration and resolution of pain recorded [135,141]. MSCs sourced from a number of tissues including synovial tissues [142][143][144][145], adipose [146,147], bone marrow [45, [148][149][150]] and blood vessels [151] have been applied in a number of applications to promote meniscal repair [44-48, [152][153][154][155][156][157][158] (Table 1). Co-cultures of meniscal cells and MSCs have also been examined in meniscal repair strategies [43, 159,160].…”