Chondrogenic Potency Analyses of Donor‐Matched Chondrocytes and Mesenchymal Stem Cells Derived from Bone Marrow, Infrapatellar Fat Pad, and Subcutaneous Fat

Abstract

Autologous chondrocyte implantation (ACI) is a cell-based therapy that has been used clinically for over 20 years to treat cartilage injuries more efficiently in order to negate or delay the need for joint replacement surgery. In this time, very little has changed in the ACI procedure, but now many centres are considering or using alternative cell sources for cartilage repair, in particular mesenchymal stem cells (MSCs). In this study, we have tested the chondrogenic potential of donor-matched MSCs derived from bone marrow (BM), infrapatellar fat pad (FP), and subcutaneous fat (SCF), compared to chondrocytes. We have confirmed that there is a chondrogenic potency hierarchy ranging across these cell types, with the most potent being chondrocytes, followed by FP-MSCs, BM-MSCs, and lastly SCF-MSCs. We have also examined gene expression and surface marker profiles in a predictive model to identify cells with enhanced chondrogenic potential. In doing so, we have shown that Sox-9, Alk-1, and Coll X expressions, as well as immunopositivity for CD49c and CD39, have predictive value for all of the cell types tested in indicating chondrogenic potency. The findings from this study have significant clinical implications for the refinement and development of novel cell-based cartilage repair strategies.

Large-scale secretome analyses unveil the superior immunosuppressive phenotype of umbilical cord stromal cells as compared to other adult mesenchymal stromal cells

“…MSCs represent a defined population of multipotent progenitor cells residing in the perivascular niche of nearly all human tissues, although different views exist (Crisan et al, 2008;Guimaraes-Camboa et al, 2017). MSC differentiation capacity and immunomodulatory properties are demonstrated in vitro, irrespective of tissue sources (Ghannam et al, 2010). However, in vitro studies show that MSCs from different origins differ in their lineage-specific differentiation capacity and their functional potential (Garcia et al, 2016;Islam et al, 2016;Subramanian et al, 2015).…”

“…MSC differentiation capacity and immunomodulatory properties are demonstrated in vitro, irrespective of tissue sources (Ghannam et al, 2010). However, in vitro studies show that MSCs from different origins differ in their lineage-specific differentiation capacity and their functional potential (Garcia et al, 2016;Islam et al, 2016;Subramanian et al, 2015). In addition, a systematic review of intra-articular injection of bone marrow MSCs in humans has concluded that articular stem cell therapies are safe (Peeters et al, 2013).…”

“…Liechty et al (2000) propose that MSCs promote tissue regeneration by engraftment of cells in damaged areas and transdifferentiation into tissue-forming cells to promote repair. Recently, paracrine signalling and release of potent bioactive factors have emerged as modulators of the microenvironment during tissue healing (Gnecchi et al, 2016;Iso et al, 2007;Prockop, 2009). In the field of cartilage repair and OA, the fate of implanted cells during biological repair procedures and their contribution to rebuilding the damaged tissue is mostly unknown.…”

Efficacy and Safety of Autologous Cell Therapies for Knee Cartilage Defects (Autologous Stem Cells, Chondrocytes or the Two): Randomized Controlled Trial Design

“…In addition, we aim to gain a better understanding of the healing response in the joint and how this differs between individuals by studying biopsy tissue from chondrocyte harvest sites, where the initial 'injury' was created under controlled conditions. Finally, we are assessing the characteristics of both cell types for predictors of potency; such analyses will include cell growth kinetics and morphological analyses as well as RNA sequencing and immunoprofiling by flow cytometry, using similar profile analyses to those we have previously published [45]. The actual markers analyzed for both techniques are constantly being updated as the study progresses to keep up to date with current literature and available technologies, future science group Efficacy & safety of autologous cell therapies for knee cartilage defects (ASCOT) Clinical Trial Protocol but regardless of this, all cells are assessed for their adherence to the International Society for Cellular Therapy profile for MSCs (i.e., positive for CD73, CD90 and CD105 and negative for CD14, CD34, CD45, CD19 and HLA-DR).…”

In vitroandin vivoperformance of methacrylated gellan gum hydrogel formulations for cartilage repair*

“…On the perspective of functional performance of cells, the risk of chondrocyte de‐differentiation, or lack of potency of the autologous chondrocytes along the need for double surgery and prolonged surgical pre‐planning, has inspired the study of alternative cell sources, including mesenchymal stromal/stem cells (MSCs) in general, and adipose‐derived stromal/stem cells (ASCs) in particular . As compared with other MSC sources, adipose tissue can be harvested with reduced morbidity at the donor site and yields of ASC are considerably high .…”