OP009 Long-term efficacy and safety of Cx601, allogeneic expanded adipose-derived mesenchymal stem cells, for complex perianal fistulas in Crohn's disease: 52-week results of a phase III randomised controlled trial

Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis

“…1 for PRISMA flow diagram). All 55 RCTs were included for review (n = 2696 patients) [18À66] ( Table 1); six of the 55 RCTs were published in abstract form only [19,45,61,64,65,67]. Included RCTs were conducted in 12 different countries and 20 (36¢4%) were multi-center [20À23, 26,27,29,38,40,46,47,49,55,62À64,66,68À70].…”

“…Patient populations were diverse and included cardiovascular (12 trials, n = 612 patients) [21,24À27,29,37,40,42,44,49,58], neurological (10 trials, n = 242 patients) [30À32, 36,45,48,57,62,65,69], renal (three trials, n = 177 patients) [55,63,67], liver (seven trials, n = 404 patients) [35,43,47,53,54,59,66], respiratory (three trials, n = 134 patients) [18,23,68] and endocrine diseases (four trials, n = 169 patients) [22,28,39,50], hematological/oncological malignancies (five trials, n = 318 patients) [33,34,41,46,71], immune deficient or inflammatory conditions (nine trials, n = 544 patients) [20,38,51,52,60,61,64,70,72], general frailty (one trial, n = 30 patients) [56], and severe sepsis in severely neutropenic patients with hematologic malignancies (one trial, n = 30 patients) [19].…”

“…With respect to MSC preparation and administration, of the 55 included RCTs, 31 (56¢4%) examined bone marrow [19,21-27,29-34,36,39,41-43,45,47,53,55À59,61,66,68,71], 16 (29¢1%) umbilical cord [28,35,38,40,44,46,[48][49][50][51][52]54,60,63,65,72], four (7¢3%) adipose-derived MSCs [18,20,62,64], two (3¢6%) placenta-derived cells [69,70]; and in two RCT (3¢6%) the source of MSCs was unclear [37,67]. See Supplementary Table 1 [33,34,41,67].…”

Review article: pathogenesis of Crohn's perianal fistula—understanding factors impacting on success and failure of treatment strategies

“…Their mechanism of action may be through induction of the activity of M2 macrophages and regulatory T‐cells and suppression of M1 macrophages, dendritic cells and cytotoxic T‐cells, rebalancing the immunological environment from inflammation to tissue repair (summarised in). The 52‐week follow‐up data show “combined remission” in 56% in the treatment arm vs 39% in the control arm . Autologous adipose‐derived stromal vascular fraction, known to demonstrate anti‐inflammatory, immunomodulatory and regenerative properties, has also been injected around Crohn's anal fistula in a Phase I‐II study with safety and modest efficacy demonstrated in small numbers and short follow‐up …”

“…week follow-up data show "combined remission" in 56% in the treatment arm vs 39% in the control arm. 86 Autologous adipose-derived stromal vascular fraction, known to demonstrate anti-inflammatory, immunomodulatory and regenerative properties, has also been injected around Crohn's anal fistula in a Phase I-II study with safety and modest efficacy demonstrated in small numbers and short follow-up. 87 Understanding and identifying mechanisms for augmenting the wound repair process is a severely understudied area and is an obvious target for future therapeutic agents.…”