Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation

Abstract

Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored.

High Tibial Osteotomy in Combination With Chondrogenesis After Stem Cell Therapy: A Histologic Report of 8 Cases

“…[11][12][13][14][15][16][17][18][19] Studies have shown success with combining arthroscopic marrow stimulation and postoperative intra-articular injections of stem cells in combination with hyaluronic acid (HA). 14,[19][20][21][22][23][24][25] We have previously published our clinical results involving a case series and a randomized controlled trial after arthroscopic subchondral drilling in combination with postoperative intra-articular injections of peripheral blood stem cells (PBSCs) and HA.…”

Histone ChIP-Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell-type specificity

“…Mesenchymal stem cells (MSCs) are able to differentiate into chondrocytes and have been used to study chondrogenesis in vitro. Tissue engineering solutions to cartilage repair include autologous chondrocyte implantation, cartilage autografts and injection of MSCs into the damaged site [16,17]. However, these methods are not widely used and complications can arise from their application.…”

Cajanine promotes osteogenic differentiation and proliferation of human bone marrow mesenchymal stem cells

“…The transforming growth factor-β (TGF-β) signal pathway has been studied as a key regulator in the self-renewal, maintenance and differentiation of stem cells. [10][11][12] It has been reported that TGF-β1 plays an important role in cartilage development and is an important chondrogenic factor. 12,13 Moreover, some studies have demonstrated that cajanine has anti-tumor and anti-oxidant functions.…”