Table 1.
Clinical studies evaluating injectable autologous intra-articular cell products without adjuvant arthroscopy/surgery (from 2016 to 2020, excluded arthroscopic and surgical interventions).
| Study (reference) | Injectable product | Study design, patients | Outcome measurements | Follow-up, results |
|---|---|---|---|---|
| SVF (cellular) | ||||
| Bansal et al.41 | (SVF + PRP), 1 injection | Case series, N = 10 patients, | WOMAC, MRI | 3, 6, 12, 18, 24 m, increased cartilage thickness >0.2 mm in six patients |
| Fodor and Paulseth42 | SVF, 1 injection | Case series, N = 6 patients, 8 knees | VAS, WOMAC, ROM, MRI | 2, 3, 6, 8, 12 m, improved clinical scores. No changes in MRI |
| Garza et al.43 | SVF, 1 injection | Prospective randomized controlled study, n = 39 1:1:1, high dose SVF: low dose SVF: placebo) | WOMAC, MRI | 6 m, 12 m, high and low SVF higher % changes in clinical outcomes than placebo; WOMAC changes: high dose 83.9%; low dose 51.5%; placebo 25%. MRI no changes |
| Hong et al.44 | SVF, 1 injection | Bilateral patients, N = 16, SVF versus HA | VAS, WOMAC, ROM | 1, 3, 6 and 12 m, VAS, WOMAC and ROM improved at 12 m in the SVF-treated knee and not in the contralateral control. Significant reduction in pain and WOMAC pain and stiffness in the SVF group (above MCID) and significant differences compared to HA-treated knees |
| Lapuente et al.45 | SVF (7 mL), 1 injection | Retrospective cohort N = 50 bilateral patients (100 knees) K–L grade III–IV | Lequesne, WOMAC, VAS, US score; biomarkers in synovial fluid | 1 year, significant improvement in clinical outcomes; decreased MMP-2, IL-1b, IL-6 and IL-8 and increased IGF-1 and IL-10 compared to baseline |
| Michalek et al.46 | SVF peri and intra-articular injection | Prospective cohort N = 29 patients older than 80 years K–L grade II–IV | Pain, analgesic consumption, KOOS | 1, 3, 6, 12, 24 m, pain improvement |
| Pintat et al.47 | (SVF + PRP) 6 mL 1 injection | Prospective cohort, Patellofemoral OA, N = 19 | WOMAC, MRI T2 | Functional improvement 6 m and 12 m, no differences in MRI at 6 m |
| Tran et al.48 | SVF | Open-label, non-randomized, phase I/II, N = 33, SVF versus placebo K–L II and III | VAS, WOMAC, MRI, Outerbridge and BME | Follow-up 24 m better outcomes in KLIII than KLII, decreased bone marrow edema |
| Microfragmented adipose tissue (tSVF) | ||||
| Ehlers et al.49 | SVF (10 mL) + PRP (8 mL) | Retrospective study (SVF + PRP) (n = 8) versus PRP (n = 29, three doses) | WOMAC | 1–3, 4–6, >6 m, PRP group improved 34%, 60% and 58%, respectively SVF group improved 51% at 4.6 month average follow-up |
| Hudetz et al.50 | Microfragmented lipoaspirate | Cohort study, N = 17, 32 knees K–L: II–IV | VAS, MRI dGEMRIC, GAG synovial profile, CRP | 3, 6, and 12 m, pain and function improvement GAG improvement in cartilage, no changes in CRP. No adverse events |
| Hudetz et al.51 | Microfragmented lipoaspirate | Cohort study, late stage OA N = 20, K–L III, n = 4, K–L IV n = 16 | MRI, VAS, WOMAC, KOOS | 12 m, clinical improvements, three patients followed TKR |
| Panchal et al.52 | Lipogems micro-fragmented adipose tissue | Cohort study, N = 17, 26 knees, K–L: 3–4 | Pain and function NPRS, LEAS, | No serious adverse events, 6 weeks, 6 and 12 m minimal clinical important differences in pain, function and quality of life |
| Peretti et al.53 | Micro-fragmented adipose tissue | Prospective randomized controlled study, N = 39, KL-III and IV | VAS pain and function | 6 m, pain reduction and functional improvement without significant differences |
| Bone marrow concentrate | ||||
| Anz et al.54 | BMC versus PRP | RCT, level II, N = 84 patients K–L: I–III BMC (n = 45) versus PRP (n = 39) | IKDC, WOMAC | 1, 3, 6, 12 m, both groups improved after 1 m and improvement was sustained during 12 m. No differences between groups. IKDC change after 12 months, 64.3% for the BMC versus 63.7%, PRP treatment; total WOMAC change 50% versus 53.2%, respectively |
| Centeno et al.55 | BMC and PRP | Controlled study, N = 48, randomized exercise therapy in the control group Patients in the exercise group (n = 22) could cross-over to BMC group at 3 m | KSS (knee society score), VAS, SF12, LEAS (lower extremity activity scale) | At 3 m all patients in exercise group crossed over to the cell group, Better clinical results in the experimental group at 6 weeks, 3,6 12 m and 24 m |
| Garay-Mendoza et al.56 | Subcutaneous G-CSF before BMA | Prospective open-label N = 61 patients, BMC versus acetaminophen | WOMAC, VAS | 1, 6 m, better outcomes in BMC group |
| Rodriguez-Fontan et al.57 | BMC from iliac crest | Knees randomized to placebo or BMC N = 19 patients, 10 knees (K–L: 1–2), (15 hips) level II | WOMAC, patient satisfaction, safety | Follow-up 6–24 months, mean 13 m Significant improvements in WOMAC |
| Shapiro and colleagues58,59 | BMC (BMAC) mixed with PPP | Level II, N = 20 bilateral patients BMC versus saline | T2 MRI mapping at 6 m, VAS, ICOAP | 1 week, 3 m and 6 m. Up to 12 m, no changes in MRI, BMC improves pain but it’s not superior to saline |
BMC, bone marrow concentrate; CRP, C-reactive protein; dGEMRIC, delayed gadolinium-enhanced magnetic resonance imaging of cartilage; GAG, glycosiaminoglycans; G-CSF, granulocyte colony stimulating factor; HA, hyaluronic acid; IKDC, International Knee Documentation Committee; K–L, Kellgren–Lawrence; KOOS, knee osteoarthritis outcome score; KSS, knee society score; LEAS, lower extremity activity scale; m, months; MRI, magnetic resonance imaging; NPRS, numeric pain rating scale; PGA, patient global assessment; SAS, short arthritis assessment scale; PPP, platelet poor plasma; PRP, platelet rich plasma; RCT, randomized controlled trial; ROM, range of motion; SF-36, short-form 36 health survey questionnaire; SVF, stromal vascular fraction; TKR, total knee replacement; T-L, Tegner–Lysholm score, VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.