Table 1.
Summary of clinical reports.
| Therapeutic Indication | Authors | Patients | Stem Cell Therapy | Control Group | Follow-Up Duration | Major Outcome Measures | Key Efficacy Results of Stem Cell Therapy |
|---|---|---|---|---|---|---|---|
| Cognitive Dysfunction Syndrome | Valenzuela et al. [42] | 6 dogs, 10–16 years old | Autologous skin-derived neural precursor cells, 0.25 × 106 cells, bilateral hippocampus injection | No treatment (media-only) | 3 months | Canine Cognitive Dysfunction Rating Scale (CCDR), pathology | Improvement in CCDR, increase in synaptic makers |
| Congestive heart failure secondary to myxomatous mitral valvular disease | Yang et al. [43] | 10 dogs, 12.8 ± 0.8 years old | Allogeneic wharton jelly derived mesenchymal stem cells (MSCs) in a 1% solution of autologous serum, 2 × 106 cells/kg, three intravenous injections | Autologous serum | 6 months | Echocardiograph, electrocardiogram (ECG), serum cardiac biomarkers, complete blood count (CBC), serum biochemical analysis, survival time, and time to first diuretic drug dosage escalation | Decreases in lymphocyte, eosinophil, and monocytes; no significant differences between groups in echocardiographic variables, ECG results, serum cardiac biomarker concentrations, survival time, and time to first diuretic drug dosage escalation |
| Myxomatous mitral valvular disease | Petchdee and Sompeewong [45] | 20 dogs, 8–15 years old | Allogeneic puppy deciduous teeth stem cells, 1 × 106 cells/kg, two intravenous injections | Standard treatment and PBS injection | 2 months | Electrocardiography, complete transthoracic echocardiography, thoracic radiography, and blood pressure | Improvements in left ventricular ejection fraction, American College of Veterinary Internal Medicine functional class, and quality of life |
| Chronic kidney disease | Thomson et al. [47] | 5 cats, 8.5–17 years old | Autologous adipose tissue derived MSCs, 1.5–6 × 106 cells, two intra-arterial injections to the kidney | None | 3 months | CBC, serum biochemistry, urinalysis, urine culture, urine protein: creatinine (UPC) ratio, blood pressure, iohexol clearance, and evaluation forms | Improvements in overall condition, decrease in polydipsia, improvements in energy and activity levels |
| Quimby et al. [48] | 10 cats, 6–17 years old | Autologous adipose tissue-derived MSCs, bone marrow-derived MSCs, different doses (1 × 105 cells, or 1 × 106 cells, or 2 × 106 cells, or 4 × 106 cells), unilateral intrarenal injection into kidney | 2 young healthy cats | Up to 4 months | Glomerular filtration rate (GFR), CBC, serum biochemistry, urinalysis, UPC ratio, and histopathology | Increase in GFR and decrease in serum creatinine in some animals | |
| Quimby et al. [49] | 21 cats, 7–18 years old | Allogeneic adipose tissue derived MSCs, 2 × 106 cells or 4 × 106 cells, three intravenous injections | No treatment | 4–8 weeks | Serum biochemistry, CBC, urinalysis, urine protein, GFR, and urinary cytokine | Decrease in serum creatinine concentrations in some animals, but not clinically relevant | |
| Quimby et al. [50] | 8 cats, 9–15 years old | Allogeneic adipose tissue derived MSCs, 2 × 106 cells/kg, three intravenous injections | Placebo | 8 weeks | Serum biochemistry, complete blood count, urinalysis, urine protein, GFR, and UPC ratio | No significant change in serum creatinine, blood urea nitrogen, potassium, phosphorus, GFR, UPC ratio, or packed cell volume | |
| Vidane et al. [51] | 9 cats, 8–16 years old | Allogeneic amniotic membrane derived MSCs, 2 × 106 cells, two intravenous injections | 1 healthy cat | 2 months | CBC, serum biochemistry parameters, urinalysis, UPC, blood gases and electrolytes | Decreases in UPC ratio and serum creatinine concentration, increases in food intake and social behavior | |
| Osteoarthritis | Wits et al. [26] | 12 dogs, 0.6–5 years old | Allogeneic adipose- tissue-derived MSCs with or without hyaluronic acid, 5 × 106 cells, intra-articular injection | Placebo | 3 months | Lameness, pain on manipulation, articular edema, range of motion, muscle atrophy, detection of crepitus on hip rotation and abduction, radiographic examination, Norberg angle measurements | Decreases in lameness at walk and pain on manipulation, improvements in range of motion and detection of crepitus on hip rotation and abduction |
| Okamoto-Okubo [27] | 16 dogs, aged 6.3 ± 3.9 and 4.6 ± 2.3 years in stem cell group and the other group | Allogeneic adipose- tissue-derived MSCs, 18 × 106 cells, two intra-articular injections | Platelet-rich plasma | 2 months | Canine Brief Pain Inventory (CBPI), the Helsinki Chronic Pain Index (HCPI), Visual Analogue Scales (VAS) for pain and locomotion, force plate gait analysis, response to palpation, descriptive numerical scale for pain | Decreases in HCPI, CBPI, VAS-pain, VAS-palp scores, as well as pain interference score and pain severity score, at 2 months | |
| Sanghani-Kerai [28] | 25 dogs, 1.5–11.5 years old | Autologous adipose tissue-derived MSCs and platelet-rich plasma, intra-articular injection | None | 6 months | Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging | Decreases in LOAD score and Asymmmetry indices, improvements in mCOAST and quality of life | |
| Shah et al. [66] | 203 dogs, 0.7–16 years old | Allogeneic adipose- tissue-derived MSCs, single intra-articular injection and/or single intravenous injection | None | 10 weeks | Symptoms (lameness and pain scores) and quality of life | Improvements in pain, mobility, daily activity, and quality of life | |
| Cabon et al. [67] | 22 dogs, 1–10 years old | Allogeneic neonatal tissues derived MSCs, 2 × 106 cells or more, 1 or 2 intra-articular injections | None | 2 years | Clinical symptoms and questionnaires | Clinical benefits | |
| Kriston-Pál et al. [68] | 58 dogs, 0.4–10 years old | Allogeneic adipose tissue derived MSCs, 12 × 106 ± 3.2 × 106 cells, intra-articular injection | None | Up to 5 years | Questionnaire (including degree of lameness) | Improvement in lameness | |
| Vilar et al. [69] | 10 dogs, 4–8 years old | Autologous adipose tissue derived MSCs, intra-articular injection | 5 healthy dogs | 6 months | Gait analysis (peak vertical force and vertical impulse) | Increases in peak vertical force and vertical impulse, but only within the first 3 months | |
| Black et al. [70] | 21 dogs, 1–11 years old | Autologous adipose-derived stem cells, 4.2 × 106 cells, intra-articular injection | Placebo | 3 months | Scores for lameness, pain, range of motion, and functional disability | Improvements in lameness, pain, and range of motion | |
| Cuervo et al. [71] | 39 dogs, 0.7–11.3 years old | Autologous adipose-derived MSCs, 30 × 106 cells, intra-articular injection | Plasma rich in growth factors | 6 months | Pain Assessment (VAS), degree of osteoarthritis, Bioarth scale assessment, quality of life | Improvements in function, pain, range of motion, and quality of life | |
| Harman et al. [72] | 74 dogs, aged 7.98 ± 3.56 and 8.59 ± 3.53 years in treatment and control groups | Allogeneic adipose-derived MSCs, 12 × 106 cells, intra-articular injection | Placebo | 2 months | Client-specific outcome measurement scoring, pain on manipulation, veterinary and owner assessment of clinical outcomes | Improvements in client-specific outcome measurement scoring, pain on manipulation, and veterinary global score | |
| Maki et al. [73] | 20 dogs, 1–14 years old | Allogeneic adipose-derived MSCs, different doses (5 × 106, or 25 × 106, or 50 × 106 cells), intra-articular injection | Placebo | 3 months | Lameness and pain; serum levels of interleukin-1 receptor antagonist protein and interleukin-10 | Improvement in lameness scores and pain in all doses; increase in serum interleukin-10 | |
| Kim et al. [74] | 55 dogs, 1–11 years old | Allogeneic umbilical- cord-derived MSCs, 7 × 106 cells, intra-articular injection | Placebo | 6 months | Force-platform gait analysis, Hudson Visual Analog Scale (HVAS) | Improvements in CBPI and HVAS scores | |
| Kriston-Pal et al. [77] | 30 dogs | Allogeneic adipose- tissue-derived MSCs in hyaluronic acid, 12 × 106 ± 3.2 × 106 cells, intra-articular injection | None | 1 year | Questionnaire (lameness), arthroscopy, histological analysis | Improvement in lameness, increase in cartilage regeneration | |
| Daems et al. [87] | 6 dogs, 5–10 years old | Xenogeneic chondrogenic induced MSCs, 1 × 106 cells, intra-articular injection | Placebo | 12 weeks | Pressure plate analysis, orthopedic examination, synovial fluid analysis, radiographic examination, owner surveys |
Improvements in pain and lameness; no significant differences in the orthopedic examination parameters, the radiographic examination, synovial fluid sampling, and pressure plate analysis between groups | |
| Elbow dysplasia | Kriston-Pal et al. [77] | 30 dogs | Allogeneic adipose- tissue-derived MSCs, 12 × 106 ± 3.2 × 106 cells, in hyaluronic acid, intra-articular injection | None | 1 year | Questionnaire (lameness), arthroscopy, histological analysis | Improvement in lameness, increase in cartilage regeneration |
| Hip dysplasia | Marx et al. [79] | 9 dogs, 0.5–12 years old | Autologous adipose-derived stem cells, 2–8 × 105 cells, or vascular stromal fractions, 2–5 × 106 cells, acupoint injection | None | 1 month | Range of motion, lameness at trot, pain on manipulation | Improvements in range of motion and lameness, decrease in pain on manipulation |
| Cranial cruciate ligament rupture | Muir et al. [80] | 12 dogs, 1.6–9.6 years old | Autologous bone- marrow-derived MSCs, 2 × 106 cells intravenous and 5 × 106 cells intra-articular injection, after tibial plateau leveling osteotomy | None | 8 weeks | Circulating T lymphocyte subsets, C-reactive protein (CRP) and cytokine concentrations in serum and synovial fluid, total nucleated cell count in synovial fluid, radiography | Decrease in serum CRP, synovial CRP, synovial interferon-gamma-Υ; increase in serum chemokine ligand 8 |
| Taroni et al. [81] | 14 dogs, 1–13 years old | Allogeneic neonatal tissues derived MSCs, 10 × 106 cells or more, intra-articular injection, after tibial plateau leveling osteotomy | Standard treatment | 6 months | Clinical score, bone healing radiographic score, semiquantitative gait evaluation | Increase in bone healing scores at 1 month; no significant difference in clinical scores and gait evaluation between the two groups at 1, 3, 6 months | |
| Santos et al. [82] | 9 dogs, 1–12 years old | Autologous adipose- tissue-derived MSCs, 1.5 × 106 cells, percutaneous injection at the osteotomy site, after tibial tuberosity advancement | No treatment (media-only) | 4 months | Radiographs (scores and analysis of the density of bone trabeculae in the spongy substance) | Increase in ossification at 1 month, but no difference for the other period | |
| Linon et al. [83] | 7 dogs | Autologous bone marrow cells, 1 × 107 cells, intra-articular injection, before tibial plateau levelling osteotomy | None | 1 year | Fluorescence microscopy of synovial membrane, synovial fluid analyses, clinical assessment | Increase in numbers of engrafted cells; improvements in lameness, function, activity, and pain on manipulation | |
| Canapp et al. [84] | 36 dogs, 1–9.5 years old | Autologous bone marrow aspirate concentrate or adipose tissue-derived progenitor cells, combined with platelet-rich plasma, intra-articular injection | None | 3 months | Orthopedic evaluation, radiograph, objective gait analysis, diagnostic stifle arthroscopy, and functional questionnaire | Improvements in stifle arthroscopy findings, total pressure index percent, and quality of life; surgery needed in some animals | |
| Supraspinatus tendinopathy | Canapp et al. [85] | 55 dogs aged 1–14 years | Autologous adipose tissue-derived progenitor cells, 5 × 106 cells, combined with platelet-rich plasma, injected into the tendon lesion | None | 3 months | Orthopedic evaluation, radiograph, magnetic resonance imaging, musculoskeletal ultrasonography, objective gait analysis, and arthroscopy | Increase in total pressure index percentage, reduction in tendon size, improvement in fiber patterns |
| Gastrocnemius tendon strain | Case et al. [86] | 1 dog, 4 years old | Autologous MSCs and orthosis, >20 × 106 cells, injected into the tendon core lesion | None | 631 days | Serial orthopedic examinations, ultrasonography, force-plate gait analysis | Improvement in lameness, increase in peak vertical force, improvement in fiber pattern |