Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas

Guadalajara, Héctor; Herreros, Dolores; De-La-Quintana, Paloma; Trébol, Jacobo; García‐Arranz, Mariano; García-Olmo, Damián

doi:10.1007/s00384-011-1350-1

Cited by 164 publications

(127 citation statements)

References 16 publications

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“…In CD, MSCs have been tested in clinical trials for two indications, namely fistulizing and luminal disease [38][39][40][41][42][43][44][45][46]. In fistulizing disease, the differentiation potential of MSCs is thought to be of crucial importance to achieve fistula tract closure.…”

Section: Msc and Ibdmentioning

confidence: 99%

“…In fistulizing disease, the differentiation potential of MSCs is thought to be of crucial importance to achieve fistula tract closure. Encouraging results from studies using locally administered MSCs to treat complex perianal fistulae support the use of this approach for patients unresponsive to infliximab [38][39][40][41][42][43][44]. For luminal disease, the rationale for the use of MSCs lies mainly in their immunosuppressive capacity.…”

Section: Msc and Ibdmentioning

confidence: 99%

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Stem cell therapy for inflammatory bowel disease

2015

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Inflammatory bowel disease (IBD) could be curable by ''immune rest'' and correction of the genetic predisposition inherent in allogeneic hematopoietic stem cell transplantation. However, balancing risks against benefits remains challenging. The application of mesenchymal stem cells (MSCs) serving as a site-regulated ''drugstore'' is a recent concept, which suggests the possibility of an alternative treatment for many intractable diseases such as IBD. Depending on the required function of MSC, such as a cell provider, immune moderator, and/or trophic resource, MSC therapy should be optimized to maximize its therapeutic benefit. Therapeutic effects do not always require full engraftment of MSCs. Therefore, optimization of pleiotropic gut trophic factors produced by MSCs, which favoring not only regulating immune responses but also promoting tissue repair, must directly enhance new drug discoveries for treatment of IBD. Stem cell biology holds great promise for a new era of cell-based therapy, sparking considerable interest among scientists, clinicians, and patients. However, the translational arm of stem cell science remains in a relatively primitive state.Although several clinical studies using MSCs have been initiated, early results suggest several inherent problems. In each study, optimization of MSC therapy appears to be the most urgent problem, and can be resolved only by scientifically unveiling the mechanisms of therapeutic action. In the present review, the authors outline how such information would facilitate the critical steps in the paradigm shift from basic research on stem cell biology to clinical practice of regenerative medicine for conquering IBD in the near future.

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Section: Msc and Ibdmentioning

confidence: 99%

Section: Msc and Ibdmentioning

confidence: 99%

Stem cell therapy for inflammatory bowel disease

2015

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“…The first one was published in 2003 [11] , and the last was published very recently, in 2013 [20] . Eight of these have been published by Spanish groups [11][12][13][14]17,[21][22][23] , two other papers come from South Korea [20,24] , and one from Italy [25] . The majority refer to ASC treatment of Crohn's disease-related fistulae.…”

Section: Treatment Outcomesmentioning

confidence: 99%

“…Complex perianal fistula without Crohn's disease Observational Autologous eASC 2 × 10 7 then 4 × 10 7 if no effect Three arms: fibrin glue, eASC, fibrin glue + eASC Guadalajara et al [23] 2012 Perianal fistula with or without Crohn's disease Observational Autologous eASC Not specified Two arms: fibrin glue, fibrin glue + eASC de la Portilla et al [17] 2012…”

Section: Acknowledgmentsmentioning

confidence: 99%

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Recurrent anal fistulae: Limited surgery supported by stem cells

García-Olmo¹,

Guadalajara²,

Rubio-Perez³

et al. 2015

WJG

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I collaborated in the analysis and interpretation of data, critically revised the main text and content, and wrote the final version of the paper; Herreros MD collaborated in design and conception of the study and performed the surgical interventions; de-la-Quintana P contributed to the first acquisition of data from patients in the outpatient clinics and their analysis; Garcia-Arranz M provided cell resources and managed all regulatory and legal aspects related to the study, participating in design and conception, and contributed to the revision of contents related to cell behavior and physiology; all authors revised and approved the final version to be published. METHODS:Under controlled circumstances, and approved by European and Spanish laws, a Compassionate-use Program allows the use of stem-cell therapy for patients with very complex anal fistulae. Candidates had previously undergone multiple surgical interventions that had failed to resolve the fistulae, and presented symptomatic recurrence. The intervention consisted of limited surgery (with closure of the internal opening), followed by local implant of stem cells in the fistula- Observational StudyORIGINAL ARTICLE tract wall. Autologous expanded adipose-derived stem cells were the main cell type selected for implant. The first evaluation was performed on the 8 th postoperative week; outcome was classified as response or partial response. Evaluation one year after the intervention confirmed if complete healing of the fistula was achieved. RESULTS:Ten patients (8 male) with highly recurrent and complex fistulae were treated (mean age: 49 years, range: 28-76 years). Seven cases were nonCrohn's fistulae, and three were Crohn's-associated fistulae. Previous surgical attempts ranged from 3 to 12. Two patients presented with preoperative incontinence (Wexner scores of 12 and 13 points). After the intervention, six patients showed clinical response on the 8 th postoperative week, with a complete cessation of suppuration from the fistula. Three patients presented a partial response, with an evident decrease in suppuration. A year later, six patients (60%) remained healed, with complete reepithelization of the external opening. Postoperative Wexner Scores were 0 in six cases. The two patients with previous incontinence improved their scores from 12 to 8 points and from 13 to 5 points. No adverse reactions or complications related to stem-cell therapy were reported during the study period. CONCLUSION:Stem cells are safe and useful for treating anal fistulae. Healing can be achieved in severe cases, sparing fecal incontinence risk, and improving previous scoring. Core tip: Our group has performed various clinical trials with adipose stem cells. Patients with very complex fistulae, multiple previous surgeries, and treatment failure are generally not able to enter these studies despite the benefit and "last chance" of cure. We present the results of a Compassionate-use Program, which enabled the application of stem-cell therapy to these patients, under strict regul...

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