One-Step Surgical Procedure for the Treatment of Osteochondral Defects with Adipose-Derived Stem Cells in a Caprine Knee Defect: A Pilot Study

Abstract

Regenerative therapies offer attractive alternatives for the treatment of osteochondral defects. Adipose-derived stromal vascular fraction (SVF) cells allow the development of one-step surgical procedures by their abundant availability and high frequency. In this pilot study we evaluated the in vivo safety, feasibility, and efficacy of this concept using scaffolds seeded with freshly isolated (SVF) or cultured adipose stem cells (ASCs), and compared these to their acellular counterparts. Osteochondral defects were created in medial condyles and trochlear grooves in knees of eight goats. Defects were filled with acellular collagen I/III scaffolds or scaffolds seeded with SVF cells or cultured ASCs. Osteochondral regeneration was evaluated after 1 and 4 months by macroscopy, immunohistochemistry, biomechanical analysis, microCT analysis, and biochemistry. After 1 month, no adverse effects were noted. Microscopic, but not macroscopic evaluation showed considerable yet not significant differences, with cell-loaded constructs showing more extensive regeneration. After 4 months, acellular constructs displayed increased regeneration, however, to a lesser degree than cell-treated constructs. The latter exhibited more extensive collagen type II, hyaline-like cartilage, and higher elastic moduli, and their glycosaminoglycan content in the cartilaginous layer better approached native tissue values. Moreover, their defect regions contained higher levels of regenerated, mature subchondral bone with more intense collagen type I staining. SVF cells tended to perform best on all parameters. In summary, this pilot study demonstrated the preclinical safety and feasibility of a one-step surgical procedure for osteochondral defect regeneration. Similar regeneration was found between freshly isolated SVF cells and cultured ASCs. Larger studies with longer follow-up are required to substantiate these findings.

Rapid Induction of Osteogenic Markers in Mesenchymal Stem Cells by Adipose-Derived Stromal Vascular Fraction Cells

“…Placing β-TCP, BMP2 and ASCs into an anterior mandibular defect also induced sufficient ossification [50], and ASCs injected into bone defects appeared to accelerate bone healing [51]. In addition, several studies of SVF application for bone generation have been reported [19, 52, 53]. Recombinant BMP2 stimulated osteoblastic differentiation in SVF cells to generate ectopic bone tissue [52], and SVF and ASCs seeded in a scaffold demonstrated a high degree of regeneration in osteochondral defects [19].…”

“…In addition, several studies of SVF application for bone generation have been reported [19, 52, 53]. Recombinant BMP2 stimulated osteoblastic differentiation in SVF cells to generate ectopic bone tissue [52], and SVF and ASCs seeded in a scaffold demonstrated a high degree of regeneration in osteochondral defects [19]. SVF supplementation on bone substitutes for maxillary sinus floor elevation (MSFE) showed potential effectiveness for bone formation [53].…”

“…SVF cells, which are traditionally isolated through enzymatic processing, contain MSCs, endothelial (progenitor) cells, immune cells, smooth muscle cells, pericytes and other stromal components [18]. SVF treatment has been shown to provide therapeutic effects similar to those of ASC treatment in osteochondral defects and myocardial infarction [19, 20], and SVF cells have been demonstrated to have similar neuroprotective effects and greater immunomodulatory properties than ASCs in experimental chronic autoimmune encephalitis studies [21]. The regenerative capacity of SVF cells has been validated in various therapeutic models, such as fat grafting, multiple sclerosis, burn injury, diabetes, radiation, Crohn’s disease, cardiac disease and bone defect models [13, 14].…”

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

“…Bone marrow-derived MSCs and adipose tissue-derived MSCs (ADMSCs) are the most applicable type of MSCs that have been used in bone regenerative medicine. Among these, the stromal vascular fraction (SVF) is a component of adipose tissue that has attracted much attention recently, specifically for the use of this fabulous extraction in bone and cartilage defects [Jurgens et al, 2013]. SVF of adipose tissue is a rich source of preadipocytes, MSCs, different types of progenitor and inflammatory cells, and cytokines, which are extracted by the processing of body fat [Gentile et al, 2012].…”

Regenerative Medicine Approaches for Treatment of Osteoarthritis

“…A cartilage defect model in sheep has shown that A-SVF has good effects that defi nitely outperform the vehicle [ 57 ]. It is thought the MSC fraction in A-SVF is primarily responsible for its benefi ts, yet A-SVF can outperform MSCs [ 57 ], indicating that other components of A-SVF may have therapeutic properties for cartilage regeneration.…”