Adipose‐Derived Regenerative Cell Transplantation for the Treatment of Hand Dysfunction in Systemic Sclerosis: A Randomized Clinical Trial

Abstract

Objective Hand dysfunction is common in systemic sclerosis (SSc). We undertook this study to evaluate the capacity of autologous adipose‐derived regenerative cells (ADRCs) to improve hand function in SSc patients. Methods The Scleroderma Treatment with Celution Processed Adipose Derived Regenerative Cells Trial was a prospective, randomized, double‐blind trial of ADRCs, in which ADRCs were obtained from patients with SSc by small‐volume adipose tissue harvest, and the fingers of each patient were injected with ADRCs. The primary end point was change in hand function at 24 and 48 weeks, assessed using the Cochin Hand Function Scale (CHFS). One of the secondary end points included the change in Health Assessment Questionnaire disability index (HAQ DI) at 48 weeks. Separate prespecified analyses were performed for patients with diffuse cutaneous SSc (dcSSc) and those with limited cutaneous SSc (lcSSc). Results Eighty‐eight patients were randomized to receive ADRCs (n = 48 [32 patients with dcSSc and 16 with lcSSc]) or placebo (n = 40 [19 patients with dcSSc and 21 with lcSSc]). Change in hand function according to CHFS score was numerically higher for the ADRC group compared to the placebo group but did not achieve statistical significance (mean ± SD improvement in the CHFS score at 48 weeks 11.0 ± 12.5 versus 8.9 ± 10.5; P = 0.299). For patients with dcSSc, the between‐group difference in the CHFS at 48 weeks was 6.3 points (nominal P = 0.069). For the secondary end point, the dcSSc group exhibited a between‐group difference of 0.17 points in the HAQ DI (nominal P = 0.044) at 48 weeks. Of the ADRC‐treated patients with dcSSc, 52% reported improvement greater than the minimum clinically important difference for both CHFS and HAQ DI compared to 16% in the placebo group (nominal P = 0.016). Small‐volume adipose tissue harvest and ADRC treatment were well tolerated. Conclusion While the primary end point of this trial was not achieved, efficacy trends were observed in patients with dcSSc. Adipose tissue harvest and ADRC injection were demonstrated to be feasible. Further clinical trials of this intervention in the setting of dcSSc are warranted.

Adipose derived stromal vascular fraction and fat graft for treating the hands of patients with systemic sclerosis. A randomized clinical trial

“…The application of decanted fat [ 27 ], centrifuged fat [ 16 ], and the ADSVF [ 10 , 17 , 24 , 34 ], has consistently and significantly improved pain, RP, and the healing of digital ulcers in the hands of patients with SSc, thereby improving their quality of life. Other inconsistently observed benefits, such as decreased digital circumferences, improvements in digital mobility and strength [ 35 ], improvements in the formation of new subungual capillaries, and improvements in function based on Cochin Functional Scale Scores, have also been reported [ 14 , 15 , 23 ]. Though, these previous studies have been uncontrolled with a short follow-up period of 6 months [ 10 , 16 , 17 ].…”

Cellular-Based Therapies in Systemic Sclerosis: From Hematopoietic Stem Cell Transplant to Innovative Approaches

“…In addition, several authors reported improved labial rhyme opening through reduced perioral fibrosis and neoproliferation of dermal capillaries [ 108 , 109 , 110 , 111 , 112 ]. More recently, two controlled trials failed to reach the primary endpoint of significant improvement of hand function in SSc patients treated with SVF [ 113 , 114 ]. Larger trials are needed to better understand the therapeutic efficacy of AT-MSCs injection on skin fibrosis of SSc patients.…”

Brown adipose tissue transplantation improves skin fibrosis in localized scleroderma

“…2,3 In recent years, adipose tissue and its derivatives have been commonly used in the clinical treatment of LoS and have achieved good therapeutic effects. [4][5][6][7][8] Structural support and biomolecules provided by autologous fat grafts effectively improved localized scleroderma-related contour irregularities and lipoatrophy. 7 Unfortunately, the high oxygen consumption of mature white adipocytes makes them unable to tolerate an ischemia-hypoxic environment, prone to apoptosis, and release many oily lipid droplets after transplantation.…”

“…Numerous studies have demonstrated that the presence of subcutaneous adipose tissue exerts a protective effect against skin fibrosis 2,3 . In recent years, adipose tissue and its derivatives have been commonly used in the clinical treatment of LoS and have achieved good therapeutic effects 4–8 . Structural support and biomolecules provided by autologous fat grafts effectively improved localized scleroderma‐related contour irregularities and lipoatrophy 7 .…”