Hip Osteoarthritis in Dogs: A Randomized Study Using Mesenchymal Stem Cells from Adipose Tissue and Plasma Rich in Growth Factors
Abstract
:1. Introduction
2. Results and Discussion
2.1. Results
2.1.1. Animal Population
2.1.2. Pain Assessment
Characteristic | aMSCs | PRGF | p-Value |
---|---|---|---|
Age (months) | 53 ± 43 (8–135) | 93 ± 35.5 (18–66) | 0.007 |
Weight | 34.9 ± 12.8 (18.3–66.2) | 36.5 ± 10.6 (20–62.8) | 0.805 |
Gender (male-female) | 10-8 | 14-3 | 0.201 |
Radiographic Osteoarthritis degree Bioarth Score * | 15.47 ± 6.02 (13.37–17.57) | 17.36 ± 3.8 (16.07–18.65) | 0.259 |
Functional limitation | 5.88 ± 2.83 (2–11) | 8.22 ± 3.39 (1–14) | 0.003 |
Joint mobility | 4.18 ± 0.63 (3–5) | 3.92 ± 0.84 (2–6) | 0.131 |
Muscle atrophy | 1.05 ± 0.55572 | 1.0526 ± 0.62126 | 0.890 |
Owner Vas Score | 28.29 ± 14.49 (6.57–72.37) | 42.55 ± 20.52 (9.21–72.37) | 0.023 |
Patients | 18 | 17 |
Variable | Time | Group | N | Mean | Std. Deviation | 95% Confidence Interval for Mean | Minimum | Maximum | p-Value between Groups | |
---|---|---|---|---|---|---|---|---|---|---|
Lower Bound | Upper Bound | |||||||||
Owner VAS | baseline | aMSCs | 34 | 28.6353 | 14.33904 | 23.6322 | 33.6384 | 6.57 | 53.94 | 0.001 |
PRGF | 36 | 42.9756 | 20.61379 | 36.0009 | 49.9503 | 9.21 | 72.37 | |||
Total | 70 | 36.0103 | 19.13089 | 31.4487 | 40.5719 | 6.57 | 72.37 | |||
1 month | aMSCs | 34 | 15.4312 | 11.03277 | 11.5817 | 19.2807 | 0.00 | 48.68 | 0.000 | |
PRGF | 36 | 27.5978 | 13.61288 | 22.9918 | 32.2037 | 5.92 | 59.21 | |||
Total | 70 | 21.6883 | 13.77408 | 18.4040 | 24.9726 | 0.00 | 59.21 | |||
3 months | aMSCs | 34 | 17.5500 | 15.87660 | 12.0104 | 23.0896 | 1.31 | 57.89 | 0.014 | |
PRGF | 36 | 27.4081 | 16.72219 | 21.7501 | 33.0660 | 4.60 | 72.37 | |||
Total | 70 | 22.6199 | 16.94175 | 18.5802 | 26.6595 | 1.31 | 72.37 | |||
6 months | aMSCs | 30 | 16.8620 | 13.55143 | 11.8018 | 21.9222 | 2.63 | 51.31 | 0.046 | |
PRGF | 34 | 24.6088 | 16.43983 | 18.8727 | 30.3450 | 0.00 | 56.58 | |||
Total | 64 | 20.9775 | 15.53332 | 17.0974 | 24.8576 | 0.00 | 56.58 | |||
Veterinarian VAS | baseline | aMSCs | 34 | 23.8200 | 10.77498 | 20.0604 | 27.5796 | 6.57 | 50.66 | 0.000 |
PRGF | 36 | 32.9692 | 9.88435 | 29.6248 | 36.3136 | 10.60 | 48.68 | |||
Total | 70 | 28.5253 | 11.23820 | 25.8456 | 31.2049 | 6.57 | 50.66 | |||
1 month | aMSCs | 34 | 14.0894 | 6.38365 | 11.8621 | 16.3168 | 6.57 | 32.89 | 0.000 | |
PRGF | 36 | 24.8964 | 7.74936 | 22.2744 | 27.5184 | 8.00 | 42.76 | |||
Total | 70 | 19.6473 | 8.91895 | 17.5206 | 21.7739 | 6.57 | 42.76 | |||
3 months | aMSCs | 34 | 10.8635 | 5.89049 | 8.8082 | 12.9188 | 3.95 | 26.31 | 0.000 | |
PRGF | 36 | 22.0383 | 7.50788 | 19.4980 | 24.5786 | 6.00 | 40.79 | |||
Total | 70 | 16.6106 | 8.76544 | 14.5205 | 18.7006 | 3.95 | 40.79 | |||
6 months | aMSCs | 32 | 9.5306 | 5.77949 | 7.4469 | 11.6144 | 3.95 | 29.60 | 0.000 | |
PRGF | 34 | 24.8297 | 8.75538 | 21.7748 | 27.8846 | 6.00 | 50.00 | |||
Total | 66 | 17.4120 | 10.68689 | 14.7848 | 20.0391 | 3.95 | 50.00 |
2.1.3. Degree of Osteoarthritis Based on the Radiographic Findings
2.1.4. Bioarth Scale Assessment
Variable | Time | Group | N | Mean | Std. Deviation | 95% Confidence Interval for Mean | Minimum | Maximum | p-Value between Groups | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Lower Bound | Upper Bound | ||||||||||||
OA degree | baseline | aMSCs | 34 | 15.47 | 6.02 | 13.37 | 17.57 | 3.00 | 21.00 | 0.259 | |||
PRGF | 36 | 17.36 | 3.80 | 16.07 | 18.65 | 10.00 | 21.00 | ||||||
Total | 70 | 16.44 | 5.06 | 15.24 | 17.65 | 3.00 | 21.00 | ||||||
1 month | aMSCs | 34 | 15.62 | 6.11 | 13.49 | 17.75 | 3.00 | 21.00 | 0.339 | ||||
PRGF | 36 | 17.36 | 3.80 | 16.07 | 18.65 | 10.00 | 21.00 | ||||||
Total | 70 | 16.51 | 5.10 | 15.30 | 17.73 | 3.00 | 21.00 | ||||||
3 months | aMSCs | 34 | 15.74 | 6.16 | 13.59 | 17.88 | 3.00 | 21.00 | 0.402 | ||||
PRGF | 36 | 17.39 | 3.81 | 16.10 | 18.68 | 10.00 | 21.00 | ||||||
Total | 70 | 16.59 | 5.12 | 15.36 | 17.81 | 3.00 | 21.00 | ||||||
6 months | aMSCs | 32 | 15.75 | 6.44 | 13.43 | 18.07 | 3.00 | 21.00 | 0.714 | ||||
PRGF | 34 | 17.18 | 3.82 | 15.84 | 18.51 | 10.00 | 21.00 | ||||||
Total | 66 | 16.48 | 5.26 | 15.19 | 17.78 | 3.00 | 21.00 | ||||||
Functional Limitation | baseline | aMSCs | 34 | 5.88 | 2.83 | 4.90 | 6.87 | 2.00 | 11.00 | 0.003 | |||
PRGF | 36 | 8.22 | 3.39 | 7.08 | 9.37 | 1.00 | 14.00 | ||||||
Total | 70 | 7.09 | 3.32 | 6.29 | 7.88 | 1.00 | 14.00 | ||||||
1 month | aMSCs | 34 | 2.85 * | 1.94 | 2.18 | 3.53 | 0.00 | 7.00 | 0.009 | ||||
PRGF | 36 | 4.56 * | 2.75 | 3.62 | 5.49 | 0.00 | 10.00 | ||||||
Total | 70 | 3.73 | 2.52 | 3.13 | 4.33 | 0.00 | 10.00 | ||||||
3 months | aMSCs | 34 | 2.26 * | 1.75 | 1.66 | 2.87 | 0.00 | 6.00 | 0.181 | ||||
PRGF | 36 | 3.33 * | 2.95 | 2.34 | 4.33 | 0.00 | 12.00 | ||||||
Total | 70 | 2.81 | 2.48 | 2.22 | 3.41 | 0.00 | 12.00 | ||||||
6 months | aMSCs | 30 | 1.80 * | 1.54 | 1.22 | 2.38 | 0.00 | 5.00 | 0.004 | ||||
PRGF | 34 | 3.71 * | 2.76 | 2.74 | 4.67 | 0.00 | 9.00 | ||||||
Total | 64 | 2.81 | 2.45 | 2.20 | 3.42 | 0.00 | 9.00 | ||||||
Joint Mobility | baseline | aMSCs | 34 | 4.18 | 0.63 | 3.96 | 4.39 | 3.00 | 5.00 | 0.131 | |||
PRGF | 36 | 3.92 | 0.84 | 3.63 | 4.20 | 2.00 | 6.00 | ||||||
Total | 70 | 4.04 | 0.75 | 3.86 | 4.22 | 2.00 | 6.00 | ||||||
1 month | aMSCs | 34 | 2.4 * | 1.23 | 1.98 | 2.84 | 0.00 | 4.00 | 0.057 | ||||
PRGF | 36 | 2.97 * | 0.88 | 2.68 | 3.27 | 1.00 | 4.00 | ||||||
Total | 70 | 2.70 | 1.09 | 2.44 | 2.96 | 0.00 | 4.00 | ||||||
3 months | aMSCs | 34 | 1.38 * | 1.52 | 0.85 | 1.91 | 0.00 | 4.00 | 0.000 | ||||
PRGF | 36 | 2.75 * | 1.02 | 2.40 | 3.10 | 1.00 | 4.00 | ||||||
Total | 70 | 2.09 | 1.45 | 1.74 | 2.43 | 0.00 | 4.00 | ||||||
6 months | aMSCs | 32 | 1.09 * | 1.40 | 0.59 | 1.60 | 0.00 | 4.00 | 0.000 | ||||
PRGF | 34 | 2.82 * | 1.00 | 2.47 | 3.17 | 1.00 | 4.00 | ||||||
Total | 66 | 1.98 | 1.48 | 1.62 | 2.35 | 0.00 | 4.00 | ||||||
Muscle Perimeter (cm) | baseline | aMSCs | 34 | 32.56 | 5.37 | 30.69 | 34.44 | 25.00 | 47.00 | 0.609 | |||
PRGF | 36 | 32.42 | 3.07 | 31.38 | 33.46 | 27.50 | 41.00 | ||||||
Total | 70 | 32.49 | 4.31 | 31.46 | 33.52 | 25.00 | 47.00 | ||||||
1 month | aMSCs | 34 | 33.51 * | 4.97 | 31.78 | 35.25 | 27.00 | 45.00 | 0.005 | ||||
PRGF | 36 | 32.56 | 3.24 | 31.46 | 33.65 | 26.00 | 40.00 | ||||||
Total | 70 | 33.02 | 4.17 | 32.03 | 34.01 | 26.00 | 45.00 | ||||||
3 months | aMSCs | 34 | 33.26 * | 4.40 | 31.73 | 34.80 | 28.00 | 43.00 | 0.984 | ||||
PRGF | 36 | 32.34 | 3.33 | 31.21 | 33.46 | 25.00 | 41.00 | ||||||
Total | 70 | 32.79 | 3.89 | 31.86 | 33.71 | 25.00 | 43.00 | ||||||
6 months | aMSCs | 32 | 33.98 * | 4.51 | 32.36 | 35.61 | 27.00 | 43.00 | 0.000 | ||||
PRGF | 34 | 32.50 | 3.35 | 31.33 | 33.67 | 26.00 | 40.00 | ||||||
Total | 66 | 33.22 | 4.00 | 32.24 | 34.20 | 26.00 | 43.00 | ||||||
Range of Motion | baseline | aMSCs | 34 | 64.12 | 12.06 | 59.91 | 68.33 | 40.00 | 90.00 | 0.000 | |||
PRGF | 36 | 75.61 | 12.22 | 71.48 | 79.75 | 54.00 | 95.00 | ||||||
Total | 70 | 70.03 | 13.37 | 66.84 | 73.22 | 40.00 | 95.00 | ||||||
1 month | aMSCs | 34 | 96.65 * | 13.21 | 92.04 | 101.26 | 60.00 | 125.00 | 0.002 | ||||
PRGF | 36 | 87.69 * | 11.71 | 83.73 | 91.66 | 55.00 | 105.00 | ||||||
Total | 70 | 92.04 | 13.16 | 88.90 | 95.18 | 55.00 | 125.00 | ||||||
3 months | aMSCs | 34 | 103.71 * | 12.26 | 99.43 | 107.98 | 60.00 | 125.00 | 0.000 | ||||
PRGF | 36 | 92.67 * | 11.35 | 88.83 | 96.51 | 68.00 | 115.00 | ||||||
Total | 70 | 98.03 | 12.96 | 94.94 | 101.12 | 60.00 | 125.00 | ||||||
6 months | aMSCs | 32 | 107.09 * | 8.56 | 104.01 | 110.18 | 90.00 | 122.00 | 0.000 | ||||
PRGF | 34 | 90.50 * | 11.24 | 86.58 | 94.42 | 60.00 | 105.00 | ||||||
Total | 66 | 98.55 | 12.99 | 95.35 | 101.74 | 60.00 | 122.00 |
Functional Limitation
Joint Mobility
Muscle Atrophy
2.1.5. Overall Satisfaction with Treatment
2.1.6. Safety Assessment
2.1.7. Requirement of Rescue Analgesia
2.2. Discussion
3. Experimental Section
3.1. Animal Population and Randomization
- ○
- aMSCs: single intra-articular injection of autologous aMSCs (DogStem®, Fat-Stem, Aalst, Belgium) (2 mL containing 30 million aMSCs) (n = 18).
- ○
- PRGF: single intra-articular injection of autologous PRGF (PRGF-Endoret®, BTI Biotechnology Institute, Vitoria-Gasteiz, Araba, Spain) (2 mL) (n = 19).
3.2. Treatments Applied
3.2.1. aMSCs
- Morphology: cells are plastic adherent, lack osmotic shrinkage, normal cell surface and fibroblastic shape.
- Ease of trypsinization: a single trypsinization.
- Color of the cultivation medium: Phenol red indicator is used to evaluate pH changes, which might affect growth of the stem cells.
- Proliferation time (doubling time): The population-doubling time (PDT) is defined as the time required for a colony area to expand twofold. Population doubling time calculates growth proliferation. PDT results are graphically visualized over passage time.
- Viability: Viability of the cells were quantified using trypan blue and cell counting methods were used.
- Cells were expanded and 30 million cells were used for clinical purpose.
3.2.2. PRGF
3.3. Outcome Variables
3.3.1. Pain Assessment
3.3.2. Bioarth Assessment Scale [82]
- Radiological assessment quantifies radiographic signs of osteoarthritis in canine elbows, hips and knees. Classifies the degrees of osteoarthritis into 4 categories 1: no signs of OA (0–2 points), 2: mild OA (3–8 points), 3: moderate OA (9–14 points), 4: severe OA (more than 14 points), based on a numerical assessment (0–3) of 7 anatomical points in the joint (limits of total score 0–21).
- Functional assessment evaluates the 3 basic functional parameters: functional limitation, joint mobility and muscle atrophy.
- ○
- Functional limitation quantifies the weight-bearing or support of each extremity, changes in posture when standing still, signs of lameness when cold and when walking, endurance during walking and playing, endurance when going up stairs and strength limitations in small jumps (measurement scale: 0 to 23 points).
- ○
- Joint mobility score is a summation of joint motion limitation, of the degree of flexion and extension of the joint studied (ROM: extension minus flexion) and pain when performing this assessment, with the goniometer (measurement scale: 0 to 7 points).
- ○
- Muscle atrophy measured in centimeters, circumference of musculature at standard anatomical references. A measure ribbon was used taking three measurements and an average calculated. (Measurement scale: 0: no atrophy, 1: mild atrophy, 2: severe atrophy).
3.3.3. Owner Satisfaction with the Treatment
- ○
- very poor
- ○
- poor
- ○
- fair
- ○
- good
- ○
- excellent
3.3.4. Safety Assessments
3.3.5. Requirement of Rescue Analgesia
3.4. Statistical Analysis
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
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Cuervo, B.; Rubio, M.; Sopena, J.; Dominguez, J.M.; Vilar, J.; Morales, M.; Cugat, R.; Carrillo, J.M. Hip Osteoarthritis in Dogs: A Randomized Study Using Mesenchymal Stem Cells from Adipose Tissue and Plasma Rich in Growth Factors. Int. J. Mol. Sci. 2014, 15, 13437-13460. https://doi.org/10.3390/ijms150813437
Cuervo B, Rubio M, Sopena J, Dominguez JM, Vilar J, Morales M, Cugat R, Carrillo JM. Hip Osteoarthritis in Dogs: A Randomized Study Using Mesenchymal Stem Cells from Adipose Tissue and Plasma Rich in Growth Factors. International Journal of Molecular Sciences. 2014; 15(8):13437-13460. https://doi.org/10.3390/ijms150813437
Chicago/Turabian StyleCuervo, Belen, Monica Rubio, Joaquin Sopena, Juan Manuel Dominguez, Jose Vilar, Manuel Morales, Ramón Cugat, and Jose Maria Carrillo. 2014. "Hip Osteoarthritis in Dogs: A Randomized Study Using Mesenchymal Stem Cells from Adipose Tissue and Plasma Rich in Growth Factors" International Journal of Molecular Sciences 15, no. 8: 13437-13460. https://doi.org/10.3390/ijms150813437