Repair of large full‐thickness articular cartilage defects by transplantation of autologous uncultured bone‐marrow‐derived mononuclear cells

Abstract

The objective of this study was to investigate the feasibility of autologous uncultured bone marrow-derived mononuclear cell transplantation in large full-thickness cartilage regeneration. After fixing with a hinged external fixator, the entire surface of the left tibial plateau was resected and large full-thickness cartilage defects were formed in 48 rabbits. Animals were divided into four groups: autologous uncultured bone marrow-derived mononuclear cells with fibrin gel (BMC), autologous uncultured peripheral blood-derived mononuclear cells with fibrin gel (PBC), fibrin gel alone (GEL), or nothing (CON) transplanted to the articular cavity 7 days after the operation. The rabbits were killed 8 or 12 weeks after the operation. The repair of defects was investigated histologically and scored using a histological and histochemical grading scale that was modified from the International Cartilage Repair Society Visual Histological Assessment Scale. To evaluate the regenerated cartilage, we also morphometrically measured the staining area positive for Safranin-O or type II collagen and calculated the percentages of the positive staining areas with respect to the regenerated soft tissue area. Histological findings showed that the BMC group had superior cartilage repair compared with the other groups, and that the PBC and CON group showed better cartilage repair than did the GEL group. Histological scores and morphometrical measurements also showed the same results quantitively. The transplantation of autologous uncultured bone marrow-derived mononuclear cells contributes to articular cartilage repair. The easy and safe method used in this study is potentially viable for clinical application.

Hydrogels for the Repair of Articular Cartilage Defects

“…64,66 MSCs differentiated into chondrocytes and produced more cartilage tissue when encapsulated in fibrin hydrogels when compared to alginate hydrogels. 67 Fibrin hydrogels have poor mechanical properties, 64,65 but they have been investigated as carriers in autologous chondrocyte transplantation in clinical trials in Europe (Tissucol).…”

Rationale for Using Direct Bone Marrow Aspirate as a Proliferant for Regenerative Injection Therapy (Prolotherapy)

“…One approach to regenerative *Address correspondence to this author at the Caring Medical and Rehabilitation Services, 715 Lake St., Oak Park IL 60301 USA; Tel: 708-848-7789; Fax: 708-848-7763; E-mail: drhauser@caringmedical.com therapy is to supply affected joints with either autologous chondrocytes or chondrogenic bone marrow-derived mesenchymal stem cells (BMSCs), prepared as a buffy coat fraction of bone marrow with or without ex vivo expansion. Recent preliminary studies support the investigation of these therapies for OA [4][5][6][7][8][9][10][11].…”

Processing Volumes and Therapeutic Cellular Doses of Point of Care Bone Marrow Concentrates

“…However, recent experimental results point towards paracrine effects as the underlying mechanism of action behind MSC [12][13] . More importantly, other differentiated cells administered along with MSC in BMC with known physiological paracrine activities might also be involved in the mode of action of this cytotherapy [14][15] . This hypothesis really shifts the initial and somehow dogmatic belief about MSC as the unique active substance in BMC opening the possibility to include other cells as therapeutic drivers.…”

“…The resulting cocktail of living cells is usually seen as simple blood but is actually a natural combination of cells from different lineages generating growth factor able to drive and module physiological regeneration processes. Therefore, many of the components within BMC have the potential to play a role by direct action stimulating endogenous resident cells or even as ancillary cells supporting the MSC´s mode of action [14,[16][17] . Here our main objective was to analyze how processing different BM volumes influenced the deliverable cellular dose and composition of BMC.…”