Enhanced Early Tissue Regeneration after Matrix-Assisted Autologous Mesenchymal Stem Cell Transplantation in Full Thickness Chondral Defects in a Minipig Model

Abstract

Adult mesenchymal stem cells (MSCs) are an attractive cell source for new treatment strategies in regenerative medicine. This study investigated the potential effect of matrix assisted MSC transplantation for articular cartilage regeneration in a large-animal model 8 weeks postoperatively. MSCs from bone marrow aspirates of eight Goettingen minipigs were isolated and expanded prior to surgery. Articular cartilage defects of 5.4 mm were created bilaterally in the medial patellar groove without penetrating the subchondral bone plate. Defects were either left empty (n = 4), covered with a collagen type I/III membrane (n = 6) or additionally treated with autologous MSC transplantation (2 x 10(6); n = 6). After 8 weeks animals were euthanized and the defect area was assessed for its gross appearance. Histomorphological analysis of the repair tissue included semiquantitative scoring (O'Driscoll score) and quantitative histomorphometric analysis for its glycosaminoglycan (GAG) and collagen type II content. All membranes were found to cover the defect area 8 weeks postoperatively. Median defect filling was 115.8% (membrane), 117.8% (empty), and 100.4% (MSC), respectively (not significant). Histomorphological scoring revealed significantly higher values in MSC-treated defects (median 16.5) when compared to membrane treatment (median 9.5) or empty defects (median 11.5; p = 0.015 and p = 0.038). Histomorphometric analysis showed larger GAG/collagen type II-positive areas in the MSC-treated group (median 24.6%/29.5% of regeneration tissue) compared to 13.6%/33.1% (empty defects) and 1.7%/6.2% (membrane group; p = 0.066). Cell distribution was more homogeneous in MSC compared to membrane-only group, where cells were found mainly near the subchondral zone. In conclusion, autologous matrix-assisted MSC transplantation significantly increased the histomorphological repair tissue quality during early articular cartilage defect repair and resulted in higher GAG/collagen type II-positive cross-sectional areas of the regenerated tissue.

In Vivo MRI Stem Cell Tracking Requires Balancing of Detection Limit and Cell Viability

“…Due to ethical concerns and In principle, whole-body scans are required after cell engraftment to detect injected cells in various organs, technical hurdles (i.e., the necessity of immunosuppression and formation of teratomas after transplantation), followed by high-resolution scans of the tissues where the cells were found. For this purpose, so far only magMSCs rather than embryonic stem cells recently came into focus for the development of regenerative cellnetic resonance imaging (MRI) meets the requirements of penetration depth, spatial resolution, repeated meabased therapies and even for the therapy of brain tumors (6,14,16,25,26,28,33,40,41). Encouraging experimental surements of individuals, and clinical availability (28,36,46).…”

Cell-based Therapies for Equine Joint Disease

“…Experimental studies using distal femoral condylar defect models in laboratory animal models (for examples, see Refs. [40][41][42][43][44] ) have generally shown an improved reparative response with MSC delivery to the defect site, but it is difficult to determine the clinical relevance of these outcomes to cartilage repair in larger and more mobile species, such as the horse.…”

Cartilage repair techniques in the knee: stem cell therapies

“…The results of this study seem to support the feasibility of a one-step procedure in a clinical setting. Jung showed that enhancement of cartilage repair with the use of collagen type I/III membrane significantly improves the repair tissue quality in minipigs [37]. In addition, use of allogenic MSC and xenoimplantation of human umbilical cord bloodderived MSC were tested in this animal model, showing induction of cartilage healing by those cell types [42,44].…”

“…With the intent of evaluation with models that is more relevant to clinical condition in humans, large animals such as pig and sheep have been used as experimental subjects [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52]. Among those, a (mini)pig model has been most frequently employed in previous studies [37][38][39][40][41][42][43][44].…”

“…Among those, a (mini)pig model has been most frequently employed in previous studies [37][38][39][40][41][42][43][44]. Various cell types and materials were tested in the studies.…”