## 4 Discussion
In our current study, the number of primary isolated cells was largest in BM samples. In addition, the number of isolated cells was also high when using the two soft tissues SM or IPF. Interestingly, the number of primary isolated cells was higher in meniscus tissue than in arthritic hyaline cartilage. Both meniscus tissue and hyaline cartilage can be accessed via anthropogenic surgery, although the limited regeneration capacity of healthy hyaline cartilage also poses ethical issues, regarding the isolation of cartilage tissue. Up to date, there is only limited research regarding the characterization of MSC-like cells derived from intraarticular ligaments and meniscal tissue. However, their qualitative multipotent differentiation capacity does not seem to differ from that of the BM-MSCs or MSC-like cells derived from hyaline cartilage. One central limitation to our study is that no experiments examining the quantitative differences of multipotent differentiation capacity were performed, meaning that all observed differences in histological and immunohistochemical stainings are highly subjective and, therefore, leave room for error. Hence, the following research should focus on examining quantitative differences, regarding multipotent differentiation of respective MSC-like cells to add to the qualitative differences presented in this study. Secondly, cumulative population doublings were highest in BM-MSCs and significantly lower in cells derived from arthritic hyaline cartilage, the ACL, and the IPF. These differences could pose a major obstacle for the clinical utilization of these MSC-like subpopulations, regarding the large amount of cells usually needed for therapeutic application. Thirdly, our current study only examined a small sample size of female patients. Earlier research has shown that differentiation capacity, proliferation capacity, and colony forming efficiency in MSCs may decline with donor age [49]. Besides, the loss of transplanted tissue and pro-inflammatory effects MSC-based cartilage repair may lead to osteophyte formation and tissue hypertrophy [17]. Further, the expression of surface antigens was only tested on cells derived from one of the five patients and did not include hematopoietic markers. However, the goal of our current study was only to show that examined cells express MSC-like surface antigens, not to compare the patterns of surface antigens between different MSC-subpopulations. Further the tissue-specific naive MSC population, situated in the natural niche within the respective tissue, differs from the MSC population that is used in conventional cell culture experiments in vitro. Before setting up differentiation experiments, the heterogeneous MSC population is isolated by plastic adherence, cell expansion is performed in the presence of FCS, and, afterwards, cells are detached by trypsinization, in order to reseed them on new cell culture dishes. All these steps influence the resulting cell population, in such a way that MSC subpopulations are enriched, which differs from their naive, original tissue-specific subpopulation. In addition, different subpopulations of MSC-like cells may require a specific set of growth factors and scaffolds to further optimize and fully examine their multipotent differentiation potential [43]. Future research should examine different growth factors and fitting biomaterials to optimize and maintain the multipotent differentiation potential of different subpopulations of MSC-like cells.