Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects
第一作者：Laurie R. Goodrich
2016-01-14 点击量：642 我要说
Background:
The chondrogenic potential of culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) is well described. Numerous studies have also shown enhanced repair when BMDMSCs, scaffolds, and growth factors are placed into chondral defects. Platelets provide a rich milieu of growth factors and, along with fibrin, are readily available for clinical use. The objective of this study was to determine if the addition of BMDMSCs to an autologous platelet-enriched fibrin (APEF) scaffold enhances chondral repair compared with APEF alone.
Methods:
A 15-mm-diameter full-thickness chondral defect was created on the lateral trochlear ridge of both stifle joints of twelve adult horses. In each animal, one defect was randomly assigned to receive APEF+BMDMSCs and the contralateral defect received APEF alone. Repair tissues were evaluated one year later with arthroscopy, histological examination, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and biomechanical testing.
Results:
The arthroscopic findings, MRI T2 map, histological scores, structural stiffness, and material stiffness were similar (p > 0.05) between the APEF and APEF+BMDMSC-treated repairs at one year. Ectopic bone was observed within the repair tissue in four of twelve APEF+BMDMSC-treated defects. Defects repaired with APEF alone had less trabecular bone edema (as seen on MRI) compared with defects repaired with APEF+BMDMSCs. Micro-CT analysis showed thinner repair tissue in defects repaired with APEF+BMDMSCs than in those treated with APEF alone (p < 0.05).
Conclusions:
APEF alone resulted in thicker repair tissue than was seen with APEF+BMDMSCs. The addition of BMDMSCs to APEF did not enhance cartilage repair and stimulated bone formation in some cartilage defects.
Clinical Relevance:
APEF supported repair of critical-size full-thickness chondral defects in horses, which was not improved by the addition of BMDMSCs. This work supports further investigation to determine whether APEF enhances cartilage repair in humans.
Repair of full-thickness articular cartilage defects continues to challenge orthopaedic surgeons. Microfracture is a first-line treatment for smaller defects, although mesenchymal stem cell transplantation has been evaluated for larger defects in animal and human studies. Investigators have used culture-expanded cells or same-day implantation of bone marrow aspirate concentrate. Tens of millions of cells may be necessary to enhance the accumulation of cartilage-like matrix.which suggests that culture expansion may be imperative to attain suitable outcomes. In a recent review of stem cell therapies for cartilage defects, it was reported that culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) had been implanted in nine of eleven clinical studies. Although some of the reports suggested beneficial results, to our knowledge no randomized controlled studies of humans have been performed to show whether implantation of BMDMSCs in chondral defects enhances outcomes.
While stem cell therapy for cartilage repair holds promise, combining BMDMSCs with additional biologics such as platelet-rich plasma may further stimulate healing. This milieu of growth factors may enhance cell viability, migration, and chondrogenic differentiation. It may also negate detrimental effects of catabolic cytokines (such as interleukin [IL]-1β derived from an inflamed joint) on cartilage. In several clinical case series, a combination of platelet-rich plasma and BMDMSCs were implanted in osteochondral defects with somewhat promising results; however, to our knowledge there have been no efforts to elucidate the individual contributions of each. Considering the potential benefits of both culture-expanded BMDMSCs and platelet-rich plasma, our objective was to answer the question of whether BMDMSCs combined with platelet-rich plasma would enhance chondral repair and regenerate hyaline cartilage when compared with platelet-rich plasma alone. Our hypothesis was that the addition of BMDMSCs to an autologous platelet-enhanced fibrin (APEF) scaffold would enhance cartilage repair compared with APEF alone when evaluated with arthroscopy, histological examination, magnetic resonance imaging (MRI), and biomechanical analysis.
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