Intra-articular transplantation of porcine adipose-derived stem cells for the treatment of canine osteoarthritis: A pilot study

Abstract

Aim: To test whether intra-articular injection of porcine adipose-derived stem cells (ADSCs) can treat canine osteoarthritis (OA).

Methods: To enroll in this study dogs must have stifle joint OA that had lasted ≥ 3 mo and been treated with OA medication without significant improvement. Three dogs fulfilled these criteria and were thus subjects for ADSCs treatment. ADSCs were isolated from abdominal adipose tissue of a 2-mo-old female Yorkshire pig. Their stem cell marker expression was examined by immunofluorescence staining. For treatment, 5 million ADSCs were injected into the diseased joint of each dog. In the next 48 h, the patient was observed for signs of inflammatory and allergic reactions. The patient was then discharged to the owner and, at 2, 6, and 12 wk, followed up with orthopedic assessment, owner questionnaire, X-ray imaging, and force-plate gait analysis.

Results: Porcine ADSCs expressed mesenchymal stem cell markers CD90 and CD105. Injection of porcine ADSCs into canine stifle joints did not cause any inflammatory or allergic reactions. Orthopedic evaluation found improvements in two dogs, particularly at the longest time point. Owners' evaluation found increased capacity and decreased pain in all three dogs' activities such as walking and running. Radiographic evaluation did not find statistically significant differences before and after treatment. Force-plate analysis found significant improvements in all three dogs after treatment.

Conclusion: Xenotransplantation of ADSCs for the treatment of OA is feasible. Further studies are needed to validate this novel treatment modality, which can then be implemented for the routine treatment of OA in veterinary medicine.

Keywords: Adipose-derived stem cells; Canine osteoarthritis; Intra-articular injection; Intra-articular transplantation; Veterinary clinical study.

Figures

Figure 1

Gait analysis platform. The platform was a 10 m × 1.22 m × 0.19 m wooden walkway and in the middle of which embedded a pressure sensor. During the analysis the dog was leash-walked by its owner from one end toward the other end of the walkway. The walking speed was recorded by two sets of photoelectric cells. The walk was repeated until three valid speeds were recorded for each leg.

Figure 2

Stem cell marker expression. Porcine adipose-derived stem cells were stained for the indicated cell markers (green) and nuclei (blue).

Figure 3

Orthopedic and owner’s evaluation. Dogs (cases 1 to 3) were evaluated by veterinarians and owners for stifle joint function and pain according to the scoring criteria listed in Tables 1 and 2. Data presented are the average and range of these scores. aP < 0.05, orthopedic score after stem cells injection vs pre-treatment (week 0); cP < 0.05, orthopedic score after stem cells injection vs the previous time point. Lower scores indicate better joint function or less pain.

Figure 4

Radiographic evaluation. X-ray images of the diseased stifle joint of each dog (cases 1 to 3) were evaluated by 5 investigators independently according to the scoring criteria listed in Table 3. Data presented are the average and range of these scores.

Figure 5

Force-plate evaluation. Dogs (cases 1 to 3) were evaluated by force-plate gait analysis as shown in Figure 1. Values of PVF and VI were obtained from three walks with valid speed. Both values were normalized for body weight; VI was further normalized for time. Data presented are the average and range of values obtained from three walks with valid speed. Unit for PVF is N kg- in percentile (kg is dog’s body weight in kilogram). Unit for VI is N s kg- (s is time in second). aP < 0.05, the week after stem cells injection vs week 0 (pre-treatment); cP < 0.05, the week after stem cells injection vs the previous time point. Higher scores indicate better joint function. PVF: Peak vertical force; VI: Vertical impulse.