Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial

Abstract

Objective Human adipose-derived mesenchymal progenitor cells (haMPCs) are stem cells with multiple differentiation potential and immunomodulatory function. Re-Join® comprises in vitro expanded haMPCs from adipose tissue of patients combined with cell suspension solution. This study was undertaken to evaluate the efficacy and safety of Re-Join® in patients with symptomatic knee osteoarthritis (OA). Methods Patients with Kellgren–Lawrence grade 1–3 knee OA were recruited from two centers and randomized to receive intra-articular injection of Re-Join® or HA. Pain and function were assessed by using WOMAC score, VAS, and SF-36. Magnetic resonance imaging (MRI) analysis was performed to measure cartilage repair. Adverse events (AEs) were collected. Results Fifty-three patients were randomized. Significant improvements in WOMAC, VAS, and SF-36 scores were observed in both groups at months 6 and 12 compared with baseline. Compared with the HA group, significantly more patients achieved 50% improvement of WOMAC and a trend of more patients achieved a 70% improvement rate in Re-Join® group after 12 months. Meanwhile, there was notably more increase in articular cartilage volume of both knees in the Re-Join® group than in the HA group after 12 months as measured by MRI. AEs were comparable between two groups. Most AEs were mild and moderate except one SAE of right knee joint infection in the HA group. Conclusions Significant improvements in joint function, pain, quality of life, and cartilage regeneration were observed in Re-Join®-treated knee OA patients with good tolerance in a period of 12 months. Trial registration ClinicalTrials.gov Identifier: NCT02162693 . Registered 13 June 2014. Electronic supplementary material The online version of this article (10.1186/s13287-019-1248-3) contains supplementary material, which is available to authorized users.

Mesenchymal stem cells - a promising strategy for treating knee osteoarthritis

“…Three studies compared MSCs with placebo, 26 – 28 and the remaining studies compared an MSC group with a control group receiving hyaluronic acid. 29 – 32 MSCs were mainly derived from bone marrow, except for two studies derived from adipose tissue 28 , 31 and one study derived from umbilical cord. 32 Three trials used autologous cells, 26 , 29 , 31 and another four trials used allogeneic cells.…”

“… 29 – 32 MSCs were mainly derived from bone marrow, except for two studies derived from adipose tissue 28 , 31 and one study derived from umbilical cord. 32 Three trials used autologous cells, 26 , 29 , 31 and another four trials used allogeneic cells. 27 , 28 , 30 , 32 The patients received cell infusions ranging from 3.9 × 10 6 to 1.5 × 10 8 cells.…”

“…Only two trials of five patients reported serious adverse events: three cases from the experimental group and two cases from the control group. 27 , 31 We counted the number of patients who reported having had mild-to-moderate adverse events in all studies. 27 , 28 , 30 – 32 No significant difference was found between the experimental group and the control group, although almost every patient experienced adverse events (p = 0.690, chi-squared test, Figure 3 ).…”

Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study

“…MSCs are adult stem cells often used to treat diseases such as graft-versus-host disease (GVHD) [5], osteoarthritis [7], autoimmune diseases [8], and liver cirrhosis [9]. Several off-the-shelf mesenchymal stem-cell therapies have been approved as drugs for some diseases.…”

Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts

“…Autologous stem cell transplants can offer a near future therapy for osteoarthritis. Mesenchymal stem cells derived from bone marrow or adipose tissue offer one potential approach for repairing cartilage tissue [6]. However, law-scale harvesting and replicative senescence limit the full utility of this approach [7,8].…”