Freitag J, Bates D, Wickham J, et al. International Journal of Regenerative Medicine, 2019.

AIM: To evaluate the efficacy of autologous adipose-derived mesenchymal stem cell (ADMSC) therapy on pain, function and disease modification in knee osteoarthritis.

METHODS: 30 participants with symptomatic knee osteoarthritis were randomized into three groups. Two treatment groups received intra-articular ADMSC therapy consisting of either a single injection (100 × 10⁶ ADMSCs) or two injections (100 × 10⁶ADMSCs at baseline and 6 months). The third group served as control and continued conservative management.

RESULTS: No serious adverse events were observed. Both treatment groups receiving ADMSCs showed clinically significant pain and functional improvement at completion of follow-up at 12 months. Radiological analysis using the Magnetic Resonance Imaging Osteoarthritis Knee Score indicated modification of disease progression.

CONCLUSION: Autologous ADMSC therapy appears to be a safe and effective therapy for knee osteoarthritis and may have the potential to prevent disease progression.

Bastos R, Mathias M, Andrade R, et al.Knee Surgery, Sports Traumatology, Arthroscopy, 2018.

PURPOSE: To compare the effectiveness and safety of intra-articular injections of autologous expanded mesenchymal stromal stem cells alone (MSCs), or in combination with platelet-rich plasma (MSCs + PRP), in patients with knee osteoarthritis.

METHODS: Eighteen patients (57.6 +/- 9.6 years) with radiographic symptomatic knee osteoarthritis (Dejour grades II-IV) were randomized to receive intra-articular injections of MSCs (n = 9) or MSCs + PRP (n = 9). Injections were performed 2-3 weeks after bone marrow aspiration (+/- 80-100 ml) which was obtained from both posterior iliac crests.

RESULTS: The Knee Injury and Osteoarthritis Outcome Score (KOOS) improved significantly throughout the 12 months for both groups (p < 0.05). No statistically significant differences between groups were found in KOOS subscales and global score improvements at 12-month end-point (n.s.). The MSCs group showed significant improvements in the pain, function and daily living activities, and sports and recreational activities subscales (p < 0.05). Similarly, the MSCs + PRP group showed significant improvements in the pain, function and daily living activities and quality of life subscales (p < 0.05). The average number of fibroblast colony forming units (CFU-F) was 56.8 + 21.9 for MSCs group and 50.7 +/- 21.7 for MSCs + PRP group. Minimal adverse effects were seen in both groups (10 adverse events, in 5 patients).

CONCLUSION: Intra-articular injections of expanded MSCs alone or in combination with PRP are safe and have a beneficial effect on symptoms in patients with symptomatic knee osteoarthritis. Adding PRP to the MSCs injections did not provide additional benefit. These results are encouraging and support the recommendation of this minimally invasive procedure in patients with knee osteoarthritis, without requiring hospitalization.

Stem Cells Translational Medicine.2019.Mautner K, Bowers R, Easley K, et al.

This study aimed to determine whether autologous orthobiologic tissue source affects pain and functional outcomes in patients with symptomatic knee osteoarthritis (OA) who received microfragmented adipose tissue (MFAT) or bone marrow aspirate concentrate (BMAC) injection. We retrospectively reviewed prospectively collected data from patients who received BMAC or MFAT injection for symptomatic knee OA. Patients completed baseline and follow-up surveys. Each survey included the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, Emory Quality of Life (EQOL) questionnaire, and Visual Analog Scale (VAS) for pain. The follow-up responses were compared with baseline for all patients and between BMAC and MFAT groups. A total of 110 patients met inclusion criteria, with 76 patients (BMAC 41, MFAT 35) and 106 knees (BMAC 58, MFAT 48) having appropriate follow-up data. The BMAC group included 17 females and 24 males, with a mean age of 59 ± 11. The MFAT group included 23 females and 12 males, with a mean age of 63 ± 11. Minimum follow-up time was 0.5 years. Mean follow-up time was 1.80 ± 0.88 years for BMAC and 1.09 ± 0.49 years for MFAT.
Both groups had significant improvement in EQOL, VAS, and all KOOS parameters pre-procedure versus post-procedure (p < .001). There was not a significant difference when comparing post-procedure scores between groups (p = .09, .38, .63, .94, .17, .15, .70, respectively).
These data demonstrate significant improvement in pain and function with both MFAT and BMAC injections in patients with symptomatic knee OA without a significant difference in improvement when comparing the two autologous tissue sources.

Kuah D, Sivell S, Longworth T, et al. Journal of Translational Medicine, 2018.

BACKGROUND: Cell therapies are being investigated as potential disease modifying treatment options for osteoarthritis (OA). Progenza (PRG) comprises in vitro expanded mesenchymal stem cells derived from human donor adipose tissue combined with cell culture supernatant. The primary objective of this first-in-human study was to evaluate the safety and tolerability of PRG.

METHODS: We conducted a single centre, randomized, double-blind, placebo-controlled, single ascending dose study. Twenty patients aged 40-65 years with symptomatic Kellgren-Lawrence grade 1-3 knee OA were treated in two cohorts and randomized 4:1 to PRG or placebo. Cohort 1: 3.9 million cells (PRG 3.9M, n = 8) or placebo (n = 2) and cohort 2: 6.7 million cells (PRG 6.7M, n = 8) or placebo (n = 2). Each patient received a single intra-articular injection and was followed-up for 12 months.

RESULTS: The study population comprised 20 patients (placebo, n = 4; PRG 3.9M, n = 8; PRG 6.7M, n = 8). All patients reported at least one treatment-emergent adverse event (TEAE). The majority of events [143/169 (84.6%)] were mild with 34 (20.1%) being considered by the investigator to be treatment related. There were no serious AEs or withdrawals due to AEs during the study. There was a statistically significant within group improvement in VAS pain scores from baseline at all timepoints for the PRG combined group, with highly significant improvements seen at months 3, 6, 9 and 12 (p <= 0.005) while VAS pain scores in the placebo group showed marginal improvement. A statistically significant improvement was also seen in WOMAC pain subscale scores from baseline at all timepoints for the PRG combined group while a marginal improvement in the placebo group was not statistically significant. Between screening and month 12, there was no decrease in average lateral tibial cartilage volume in the PRG 3.9M group while the placebo group showed a statistically significant cartilage loss. This difference between the placebo and PRG 3.9M group was statistically significant (LSM difference 106.47 mm³, 95% CI 13.56 mm³, 199.37 mm³, p = 0.028).

CONCLUSION: When administered as a single intra-articular injection to patients with symptomatic knee OA, PRG was safe and well tolerated. Furthermore, measurable improvements in symptoms and knee structure outcomes warrant further studies on PRG's potential for disease modification in OA