Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn’s Disease

Panés, Julián; Garcı́a-Olmo, Damián; Assche, Gert Van; Colombel, Jean Fréd́eric; Reinisch, Walter; Baumgart, Daniel C.; Dignaß, Axel; Nachury, Maria; Ferrante, Marc; Kazemi-Shirazi, Lili; Grimaud, J. C.; Portilla, Fernando de la; Goldin, Eran; Richard, M; Díez, Mary Carmen; Tagarro, Ignacio; Leselbaum, Anne; Danese, Silvio; Stift, Anton; Tschmelitsch, Jörg; Mrak, Karl; Tilg, Herbert; Kroberger, Irmgard; D’Hoore, André; Looze, Danny De; Baert, Filip; Pattyn, Paul; Zerbib, Philippe; Zerbib, Frank; Viennot, Stéphanie; Dupas, Jean‐Louis; Orsoni, P; Hébuterne, Xavier; Rahili, Amine; Allez, Matthieu; Panís, Yves; Reinshagen, Max; Scherer, Roland; Sturm, Andreas; Kruis, Wolfgang; Duek, D; Waterman, Matti; Lahat-zok, Adi; Zmora, Oded; Tulchinsky, Hagit; Edden, Yair; Spinelli, Antonino; Annese, Vito; Angriman, Imerio; Riegler, G.; Selvaggi, Francesco; Oldenburg, Bas; Gilissen, Lennard P L; Montfort, G; Löwenberg, Mark; Bemelman, Adrianus Willem; Almenara, R; Arranz, María Dolores Martín; García-Arranz, Mariano; Gisbert, Javier P.; Palasí, Rosana; Samsó, Carlos Taxonera; Justiniano, José Manuel Herrera; Rada, Ricardo; Butrón, Ma Teresa; López, Daniel Carpio; López-Sanromán, Antonio; Val, J.; Solana, Amparo; González‐Argente, Francesc Xavier; Pastor, C. Martínez; Guadalajara, Héctor

doi:10.1053/j.gastro.2017.12.020

Cited by 330 publications

(271 citation statements)

References 33 publications

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“…Hence, the final results indicate that on long‐term evaluation, twice as many patients treated using autologous ASCs plus fibrin glue had a fully cured fistula, in comparison with fibrin glue alone (50% ASC group vs 26% control group). These improved results on the long‐term assessment reflect the long‐term results of the previous phase II and phase III (FATT‐1) RCTs and from other clinical trials in Crohn disease using allogeneic ASCs and reporting on long‐term assessment . These long‐term improvements can be explained by the biological action of these types of cells …”

Section: Discussionsupporting

confidence: 73%

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Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

García‐Arranz

García-Olmo

Herreros

et al. 2019

Stem Cells Translational Medicine

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The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose‐derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single‐blind clinical trial, recruiting 57 patients. Forty‐four patients were categorized as belonging to the intent‐to‐treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re‐epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long‐term and sustained fistula healing.

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Section: Discussionsupporting

confidence: 73%

“…In addition, control of the cell implant was not exhaustive, causing high injection speed and not always in the appropriate areas . Later, a phase III clinical trial in Crohn perianal fistula using allogeneic ASCs showed a clear advantage when using these cells over the control group, particularly in long‐term evaluation …”

Section: Introductionmentioning

confidence: 99%

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

García‐Arranz

García-Olmo

Herreros

et al. 2019

Stem Cells Translational Medicine

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“…More recently, mesenchymal stem cell treatment has shown promising results compared to standard medical treatment; however, the fistula closure rates in those patients treated with placebo confirm that a good surgical approach plays a key role on the resolution of CD‐pAF. Moreover, these data indirectly suggest that multimodality treatment (surgery + medical therapy) may be the best approach in the short term for these patients, although no direct evidence on large populations of patients is currently available …”

Section: Discussionmentioning

confidence: 99%

“…However, so far no convincing data on these interventions are available, and many of these agents are not approved or reimbursed for active perianal CD. Finally, we did not evaluate patients who received mesenchymal stem cell therapy which is showing promising results in fistula healing …”

Section: Discussionmentioning

confidence: 99%

The role of multimodal treatment in Crohn′s disease patients with perianal fistula: a multicentre retrospective cohort study

Scheer

Black

Pugliese³

et al. 2018

Aliment Pharmacol Ther

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“…Clinical translation cannot be realized without also considering investor expectations in relation to the product potential and its possible therapeutic impact. For this reason economic factors have been also influencing the field: when an MSC‐based product has been showing a valid safety and therapeutic profile, corporate investments raise making product available for many . However, when product retains uncertainties that are not challenged within adequate preclinical models followed by well‐designed clinical trials, venture capital and big pharma may be generally reluctant to invest.…”

Section: Business Costs and Mscs Clinical Translationmentioning

confidence: 99%

Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review

Mastrolia

Foppiani

Murgia

et al. 2019

Stem Cells Translational Medicine

186

158

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Summary Identified 50 years ago, mesenchymal stromal/stem cells (MSCs) immediately generated a substantial interest among the scientific community because of their differentiation plasticity and hematopoietic supportive function. Early investigations provided evidence of a relatively low engraftment rate and a transient benefit for challenging congenital and acquired diseases. The reasons for these poor therapeutic benefits forced the entire field to reconsider MSC mechanisms of action together with their ex vivo manipulation procedures. This phase resulted in advances in MSCs processing and the hypothesis that MSC‐tissue supportive functions may be prevailing their differentiation plasticity, broadening the spectrum of MSCs therapeutic potential far beyond their lineage‐restricted commitments. Consequently, an increasing number of studies have been conducted for a variety of clinical indications, revealing additional challenges and suggesting that MSCs are still lagging behind for a solid clinical translation. For this reason, our aim was to dissect the current challenges in the development of still promising cell types that, after more than half a century, still need to reach their maturity. Stem Cells Translational Medicine 2019;8:1135–1148

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Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn’s Disease

Cited by 330 publications

References 33 publications

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

The role of multimodal treatment in Crohn′s disease patients with perianal fistula: a multicentre retrospective cohort study

Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review

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