Clinical and laboratory findings following transplantation of allogeneic adipose-derived mesenchymal stromal cells in knee osteoarthritis, a brief report

Sadri, Bahareh; Tamimi, Atena; Nouraein, Shirin; Bagherifard, Abolfazl; Mohammadi, Javad; Mohammadpour, Mehdi; Hassanzadeh, Mohammad; Bajouri, Amir; Madani, Hoda; Barekat, Maryam; Torshizi, Shahedeh Karimi; Malek, Mahrooz; Liastani, Maede Ghorbani; Maal, Alireza Beheshti; Niknejadi, Maryam; Vosough, Massoud

doi:10.1080/03008207.2022.2074841

Cited by 9 publications

(7 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After the safety approval which was obtained in the phase I by the assessment and monitoring of three patients [ 23 ], phase II was conducted and 40 patients enrolled in two distinct groups, 20 patients at the AD-MSCs group received an intra-articular single dose of 100 × 10 6 AD-MSCs suspended in 5 ml normal saline (NS), and 20 patients in the control group received 5 ml NS. The patients underwent a single injection of 100 × 10 6 AD-MSCs in this study; this cell dose has been chosen after the review of some dose escalation studies [ 24 , 25 ] which declared that high dose (100 × 10 6 ) of MSCs transplantation led to more enhancement in clinical and MRI outcomes compared to low or medium dose.…”

Section: Methodsmentioning

confidence: 99%

“…The standard operating procedure for allogeneic AD-MSCs isolation, preparation, and characterization was applied according to GMP regulation at CellTech Pharmed Co. as IR-FDA certified cell production facility same as our previous study [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

“…In this study, following our previous pilot study which evaluated the clinical and laboratory findings of AD-MSCs transplantation in KOA [ 23 ], we present a phase II triple-blinded randomized clinical trial for the evaluation of the efficacy of AD-MSCs for the treatment of KOA.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial

et al. 2023

Self Cite

View full text Add to dashboard Cite

Background Intra-articular injection of mesenchymal stromal cells (MSCs) with immunomodulatory features and their paracrine secretion of regenerative factors proposed a noninvasive therapeutic modality for cartilage regeneration in knee osteoarthritis (KOA). Methods Total number of 40 patients with KOA enrolled in two groups. Twenty patients received intra-articular injection of 100 × 106 allogeneic adipose-derived mesenchymal stromal cells (AD-MSCs), and 20 patients as control group received placebo (normal saline). Questionnaire-based measurements, certain serum biomarkers, and some cell surface markers were evaluated for 1 year. Magnetic resonance imaging (MRI) before and 1 year after injection was performed to measure possible changes in the articular cartilage. Results Forty patients allocated including 4 men (10%) and 36 women (90%) with average age of 56.1 ± 7.2 years in control group and 52.8 ± 7.5 years in AD-MSCs group. Four patients (two patients from AD-MSCs group and two patients from the control group) excluded during the study. Clinical outcome measures showed improvement in AD-MSCs group. Hyaluronic acid and cartilage oligomeric matrix protein levels in blood serum decreased significantly in patients who received AD-MSCs (P < 0.05). Although IL-10 level significantly increased after 1 week (P < 0.05), the serum level of inflammatory markers dramatically decreased after 3 months (P < 0.001). Expressions of CD3, CD4, and CD8 have a decreasing trend during 6-month follow-up (P < 0.05), (P < 0.001), and (P < 0.001), respectively. However, the number of CD25+ cells increased remarkably in the treatment group 3 months after intervention (P < 0.005). MRI findings showed a slight increase in the thickness of tibial and femoral articular cartilages in AD-MSCs group. The changes were significant in the medial posterior and medial anterior areas of the tibia with P < 0.01 and P < 0.05, respectively. Conclusion Inter-articular injection of AD-MSCs in patients with KOA is safe. Laboratory data, MRI findings, and clinical examination of patients at different time points showed notable articular cartilage regeneration and significant improvement in the treatment group. Trial registration: Iranian registry of clinical trials (IRCT, https://en.irct.ir/trial/46), IRCT20080728001031N23. Registered 24 April 2018.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…A study by Li et al demonstrated systemic anti-inflammatory effects of MSC(M) injections and platelet lysate (three monthly injections with MSCs and platelet lysate injected three days apart) relative to arthroscopic debridement and HA injections in knee OA patients (KL grade 0–2, N = 40–46/group); significant reductions in serum TNF-α and IL-6 were noted within the MSC(M)-treated group at 6 and 12 months relative to baseline and to the HA controls [ 120 ]. In a three-patient study, Sadri et al also reported a trend toward decreased serum IL-6 and transiently increased IL-10 in knee OA patients (KL grade 2–3) receiving allogeneic MSC(AT), albeit with a limited sample size and no statistical testing [ 121 ].…”

Section: Msc Mechanisms Of Action In Knee Oamentioning

confidence: 99%

“…There is limited clinical evidence on MSC mechanisms of action in OA. Recent clinical data have supported immunomodulation as a relevant mechanism of action for MSCs in OA [ 119 – 121 , 127 ], but more research is needed to understand the systemic and local effects of intra-articular MSC injections on cellular and humoral immune responses. Clinical trials have shown that MSCs may exert cartilage reparative and/or chondroprotective effects on OA, as evidenced by imaging, second-look arthroscopy, histology, and biomarker analyses; however, additional higher-powered and controlled studies are needed to confirm these findings.…”

Section: Msc Mechanisms Of Action In Knee Oamentioning

confidence: 99%

Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success

2023

View full text Add to dashboard Cite

Osteoarthritis (OA) is a degenerative multifactorial disease with concomitant structural, inflammatory, and metabolic changes that fluctuate in a temporal and patient-specific manner. This complexity has contributed to refractory responses to various treatments. MSCs have shown promise as multimodal therapeutics in mitigating OA symptoms and disease progression. Here, we evaluated 15 randomized controlled clinical trials (RCTs) and 11 nonrandomized RCTs using culture-expanded MSCs in the treatment of knee OA, and we found net positive effects of MSCs on mitigating pain and symptoms (improving function in 12/15 RCTs relative to baseline and in 11/15 RCTs relative to control groups at study endpoints) and on cartilage protection and/or repair (18/21 clinical studies). We examined MSC dose, tissue of origin, and autologous vs. allogeneic origins as well as patient clinical phenotype, endotype, age, sex and level of OA severity as key parameters in parsing MSC clinical effectiveness. The relatively small sample size of 610 patients limited the drawing of definitive conclusions. Nonetheless, we noted trends toward moderate to higher doses of MSCs in select OA patient clinical phenotypes mitigating pain and leading to structural improvements or cartilage preservation. Evidence from preclinical studies is supportive of MSC anti-inflammatory and immunomodulatory effects, but additional investigations on immunomodulatory, chondroprotective and other clinical mechanisms of action are needed. We hypothesize that MSC basal immunomodulatory “fitness” correlates with OA treatment efficacy, but this hypothesis needs to be validated in future studies. We conclude with a roadmap articulating the need to match an OA patient subset defined by molecular endotype and clinical phenotype with basally immunomodulatory “fit” or engineered-to-be-fit-for-OA MSCs in well-designed, data-intensive clinical trials to advance the field.

show abstract

Exploring Orthopedic Stem-Cell Approaches for Osteoarthritis Management: Current Trends and Future Horizons

Ehioghae,

Vippa,

Askins

et al. 2023

Curr Pain Headache Rep

View full text Add to dashboard Cite

Clinical and laboratory findings following transplantation of allogeneic adipose-derived mesenchymal stromal cells in knee osteoarthritis, a brief report

Cited by 9 publications

References 45 publications

Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial

Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial

Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success

Exploring Orthopedic Stem-Cell Approaches for Osteoarthritis Management: Current Trends and Future Horizons

Contact Info

Product

Resources

About