The question of the efficacy of stem cell treatments is a topic of great current (October 2020) interest with randomized clinical trials on-going or planned for a variety of conditions.
This 2020 publication is a systematic review of studies of mesenchymal stromal cell-based therapies for the treatment of osteoarthritis.
Maleitzke T, Elazaly H, Festbaum C, et al. Mesenchymal Stromal Cell-Based Therapy-An Alternative to Arthroplasty for the Treatment of Osteoarthritis? A State of the Art Review of Clinical Trials. J Clin Med. 2020;9(7):2062. Published 2020 Jun 30. doi:10.3390/jcm9072062
The review provides a description of studies of mesenchymal stromal cell-based therapies for treatment of osteoarthritis that are registered at ClinicalTrials.gov and are currently recruiting along with their registration numbers. Review of these registered and recruiting trials gives an idea of the scope of interest in these therapies for one condition—osteoarthritis—as well as the diversity of approaches.
The review identified published randomized placebo-controlled trials of mesenchymal stromal cell treatments for osteoarthritis as well as randomized trials with an active treatment comparison and non-randomized studies (sometimes called trials but not really trials). These are described in Table 2 of the cited publication.
The authors do not try to meta-analyze data from these published studies. Nor do they draw conclusions about whether mesenchymal stromal cell treatments should or should not be used to treat osteoarthritis.
Two studies cited in this review (reference 83 and 103) seem to address the question of whether there are any randomized trials that show benefits of mesenchymal cell-based therapies for any condition. There are.
FREITAG, BATES, WICKHAM et al.
Reference 83 is a reference to a study of adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis.
Freitag J, Bates D, Wickham J, et a. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med. 2019;14:213-230. doi: 10.2217/rme-2018-0161. Epub 2019 Feb 14. PMID: 30762487.
The article is available in full-text form for free. The link is accessed from PubMed.
The trial was registered on the Australian and New Zealand Clinic Trial Registry (Trial ID: ACTRN12614000814673).
There were 30 patients in the trial. They were randomized to three groups with 10 patients in each group—a single intra-articular injection of 108 (100 million) mesenchymal cells, two injections of 108 (100 million) mesenchymal cells six months apart, and a control (ongoing conventional conservative management only). The mesenchymal cells were autologous—derived from the treated persons own adipose tissue. The participants were not blinded to their treatment assignment. Randomization was “prepared in advance using a random number generator.” However, researchers with direct involvement in participant recruitment and treatment were blinded to the randomization process.
In spite of random assignment, participants in the control group had a lower body mass index than participants in the treatment groups (25.2 for control compared with 31.6 in the group given 1 injection and 30.4 in the group given two injections).
Follow-up was done at 1, 3, 6 and 12 months.
Main results for pain and function were as follows:
“Pain, as measured by the NPRS [Numeric Pain Rating Scale], in the
one-injection group and two-injection group improved from a mean
(standard deviation) of 6.7 (1.7) and 6.5 (1.4) to 2.6 (1.8) and 2.3
(2) respectively at completion of the study. Within group improvement
when compared with baseline was statistically significant (< 0.05)
throughout all time points in both the single and two injection
protocol treatment groups. Similarly, between group differences
revealed that both the one-injection and two-injection groups had
significantly less pain at 12 months compared with the Control group.
No significant differences were found between the two treatment
“KOOS [Knee Injury and Osteoarthritis Outcome Score] subscale analysis
showed consistent improvement in all subscales during follow-up and
this was maintained until completion of follow-up at 12 months. There
was no significant difference at 12 months in all subscales between
the two treatment groups. All subscales displayed statistically
significant improvement against control at 12 months of follow-up. The
one-injection group had more consistent improvement against Control
throughout the follow-up period.”
MATAS, ORREGO, AMENABAR et al.
Reference 103 is a reference to a study of adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis.
Matas J, Orrego M, Amenabar D, et al. Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial. Stem Cells Transl Med. 2019;8(3):215-224. doi:10.1002/sctm.18-0053
The full-text can be accessed on PMC.
The study was registered at Clinical Trials.gov (NCT02589695). It was a randomized, double-blind study of a single versus repeated (two) injections of umbilical-derived mesenchymal stromal cells compared with compared with standard therapy--repeated (two) injections of intra‐articular hyaluronic acid—in patients with knee OA.
There were 29 patients in the trial. They were randomized to three groups—10 were allocated to receive a single intra-articular injection of 20 x 106 (20 million) umbilical-derived mesenchymal cells at baseline and a plasma/saline placebo injection at six month; 10 were allocated to receive a baseline intra-articular injection of 20 x 106 (20 million) umbilical-cord mesenchymal cells and another injection of 20 x 106 (20 million) cells at six months; 9 were allocated to receive two intra-articular injections of hyaluronic acid--one at baseline and another at six months. There was 1 drop-out in each of the three groups leaving 9 patients in the single injection group, 9 in the two injection group, and 8 in active treatment comparator.
The mesenchymal cells were allogenic—derived from the umbilical cords obtained from full‐term human placentas by cesarean section after informed consent.
The investigators and the participants were blinded to their treatment assignment. Randomization was described as being “by electronic data entry system.”
Follow-up was done at 1, 4, 8, 12, 24, 36, and 52 weeks.
Pain and function outcomes were assessed using a number of instruments-- the Western Ontario and Mc Master Universities Arthritis Index (WOMAC), the Pain Visual Analog scale (VAS), the Short‐form 36 (SF‐36) questionnaire, the Patient Global Assessment, and the Outcome Measures in Rheumatology Committee (OMERACT)‐Osteoarthritis Research Society International (OARSI) Responder Index Criteria .
Results were reported for the Western Ontario McMaster Universities Arthritis Index, the Pain Visual Analogue Scale, the SF-36, and Outcomes Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARS) Responder Index.
Results were as follows:
At 12 months follow‐up, scores on the pain subscale of the WOMAC‐A were statistically lower [better] in the group treated with 2 mesenchymal stromal cell injections (1.1 ± 1.3) compared with the group treated with hyaluronic acid (4.3 ± 3.5). (Table 3) (p = 0.04 after correction for multiple comparison)
Considering the total WOMAC, at 12 months, the group treated with 2 mesenchymal stromal cell injections also had statistically significantly lower [better] scores than the group with hyaluronic acid at 12 months (4.2 ± 3.9 vs. 15.2 ± 11). (Table 3) (p = .05 after correction for multiple comparisons).
At 12 months, scores on the pain VAS were statistically significantly lower [better] in the group treated with two mesenchymal stromal cell injections compared with group treated with hyaluronic acid (2.4 ± 2.1 vs. 22.1 ± 9.8). (Table 3) (p = .03 after correction for multiple comparison).
There were no statistically significant differences between the three groups on functional component of the WOMAC or the SF-36.
The authors also reported that:
“When comparing how often patients in the trial would achieve
responder status at study endpoint, as defined by the OMERACT‐OARSI
responder index criteria, all individuals in the repeated MSC (two
injections of mesenchymal stromal cell) group were found to be
responders as opposed to 62.5% of patients in the control HA group, a
tendency that did not reach significance (p = .08; Figure 3D).”
So the answer to your question is yes, there are randomized controlled trials—with one being blinded--that report benefits of mesenchymal stromal cell (stem cell) treatment for knee osteoarthritis.
Given the small number of patients in these two trials and the findings in other randomized trials, these findings should NOT be used as evidence that the treatments studied in these two trials, or any other stem cell treatment, are recommended for any patient with knee osteoarthritis (or any other condition).