Fate of donor bone marrow cells in medial collateral ligament after simulated autologous transplantation

Abstract

A potential strategy to enhance ligament healing by transplantation of mesenchymal stem cells (MSCs), which are demonstrated to differentiate into fibroblast-like cells in vitro, is presented. The objective of this study was to follow transplanted nucleated cells from bone marrow, which contain MSCs, in the healing medial collateral ligament (MCL) over time, and to examine their phenotype and survivability. It was hypothesized that MSCs in nucleated cells from bone marrow would differentiate into fibroblast-like cells in the healing ligament following adaptation to the environment. The transplantation model employed in this study eliminates the immune response to a donor by the recipient using a transgenic rat (donor), which does not produce foreign protein from transgenes, and its wild-type rat (recipient) in order to simulate autologous transplantation. The MCL of the wild-type rat was ruptured, where 1 x 10(6) nucleated cells of bone marrow from the transgenic rat were injected. The transgenes in transplanted nucleated cells were detected throughout the healing MCL for 28 days by in situ hybridization. At 3 days, many donor cells were evident in the injury site and fascial pocket, and some were found in the midsubstance. Morphologically, transplanted cells with elongated nuclei were found at the ruptured edge of the midsubstance and surface of the unruptured site after 3 days. At 28 days, these cells continued to survive in the healing MCL. Their shapes were similar to those of surrounding recipient MCL fibroblasts. Thus, transplanted cells might differentiate into fibroblasts. Therefore, it was demonstrated that there is a potential for nucleated cells from bone marrow to serve as a vehicle for therapeutic molecules as well as to be a source in enhancing healing of ligaments.

Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament

“…There are several reports that have used different cell types to treat ligament injury such as myoblasts, bone marrow cells and mesenchymal stromal cells. 27,34,35 In the present study, we demonstrated that nLacZ transduced MDSCs could survive after being transplanted into an MCL injury site and that mRNA expression of rCol1A2 and rTeM were higher in the ligaments injected with MDSCs transduced with VEGF when compared to the MDSC transduced with sFLT1 and MCLs injected with PBS. From these results, we confirmed that MDSCs could contribute to ligament healing and that blocking VEGF with sFLT1 impedes the healing process.…”

“…21 The surgical procedure was performed based on a method previously described. 26,27 Briefly, under anesthesia, the MCL and the fascia covering the MCL were transected by sharply cutting the midsubstance. Next, the fascia was sutured to make a fascial pocket in order to keep the cells in place.…”

Adjuvant neuropeptides can improve neuropathic ligament healing in a rat model

“…However, stem cell augmentation has yet to show more than slight improvement in mechanical properties to the healing ligament. 35,36 Alternatively, increased hemorrhage at the site of MCL healing significantly improves strength. Wright et al increased failure force to 70% of intact after 28 days of healing by increasing hemorrhage at the injury site.…”

What We Should Know Before Using Tissue Engineering Techniques to Repair Injured Tendons: A Developmental Biology Perspective

“…Several studies have attempted to use biological treatments to repair injured tendons (Table 1). 86,104,106,[108][109][110][111][112][113][114][115][116][117][118][119] However, the efficiency of the restoration from these treatments is unsatisfying. Many potential factors have been implicated in tendon formation, but how they interact and regulate to generate a functional tendon remains to be discovered.…”