Treatment of cranial cruciate ligament injuries in dogs using a combination of tibial tuberosity advancement procedure and autologous mesenchymal stem cells/multipotent mesenchymal stromal cells – A pilot study

Abstract

In the present pilot study, we evaluated different supplemental therapies using autologous multipotent mesenchymal stromal cells (MMSCs) for the treatment of cranial cruciate ligament defects in dogs. We used tibial tuberosity advancement (TTA) and augmented it by supportive therapy with MMSCs in three patient groups. In the first patient group, the dogs were injected with MMSCs directly into the treated stifle one month after surgery. In the second group, MMSCs were delivered in a silk fibroin scaffold which was placed in the osteotomy gap during surgery. In the third group, MMSCs were first mixed with bone tissue and blood from the patient and delivered into the osteotomy gap during surgery. In the control group, patients underwent the TTA procedure but did not receive MMSC treatment. In the group of patients who received cells in the silk fibroin scaffold during surgery, the osteotomy gap did not heal, presumably due to the low absorption of silk fibroin. Patients who received MMSCs mixed with bone tissue and blood during surgery into the osteotomy gap recovered clinically faster and had better healing of the osteotomy gap than dogs from the other two treated groups and from the control group, as assessed by clinical examination and quantification of radiographs. In conclusion, dogs that received stem cells directly into the osteotomy gap (Group 3) recovered faster compared to dogs from Groups 1 (MMSCs injected into the joint one month after surgery), 2 (cells implanted into the osteotomy gap in a silk fibroin scaffold), and the control group that did not receive additional MMSCs treatment.

Could an Anterior Cruciate Ligament Be Tissue-Engineered from Silk?

“…A chitosan-silk-PET-HA-silver combination showed promising results supporting cell growth [19]. When ACL reconstructions were combined with tibial tuberosity advancements in dogs, silk/MSCs preparations stimulated the bone healing of osteotomy injuries [154]. Silk fibroin collagen scaffolds combined with MSCs stimulated bone integration after ACL reconstruction in a rabbit model [26].…”

Manufacturing Mesenchymal Stromal Cells for the Treatment of Osteoarthritis in Canine Patients: Challenges and Recommendations

“…The clinical application of MSC-based therapy in veterinary medicine comprises of multiple target diseases, with the vast majority being focused on musculoskeletal conditions such as osteoarthritis (8,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34), cruciate ligament disease (9,(35)(36)(37)(38), hip dysplasia (39), bone fractures and lesions (40,41), muscle tears (42,43) and tendinopathies (44,45). Canine clinical studies have also shown promising results for the treatment of diseases of the gastro-intestinal tract (46)(47)(48), central nervous system (49)(50)(51)(52)(53), cardiovascular system (54,55), cutaneous (56)(57)(58)(59) and ocular conditions (60)(61)(62)(63), resulting in encouraging safety and efficacy data (Figure 2).…”

Therapeutic Effect of Exosomes Derived From Stem Cells in Spinal Cord Injury: A Systematic Review Based on Animal Studies

“…The main reasons are the low survival rate of stem cell transplantation, limited targeting ability, difficulty in passing through the blood-brain barrier, prone to immune rejection, dedifferentiation, formation of malignant tumor formation, etc. ( 5 , 6 ). In addition, some studies have revealed that the transplantation efficiency of stem cells is extremely low, where only 1% of the transplanted stem cells can migrate to the target tissue.…”