Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn's disease: a new cell-based therapy

Garcı́a-Olmo, Damián; García‐Arranz, Mariano; García, Lourdes Gómez; Cuellar, Eduardo; Blanco, Ignacio Fernández; Prianes, Luis Asensio; Montes, J. A. Rodríguez; Pinto, Francisca; Marcos, Dolores Herreros; García‐Sancho, Luis

doi:10.1007/s00384-003-0490-3

Cited by 286 publications

(162 citation statements)

References 8 publications

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“…To date, there are 11 published papers including data on stem cell-based treatment of anal fistulae ( Table 2). 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] .…”

Section: Treatment Outcomesmentioning

confidence: 99%

“…According to current regulatory issues at the time (2002), our team started a clinical trial process in order to test the ability of adipose-derived stem cells (ASC) to improve healing in complex perianal fistulae, including those associated with Crohn's disease. The chosen cell source was adipose tissue because the harvesting process for ASC following liposuction was simple and could be performed in our on-site laboratory [11] . To the date, we have finished a complete clinical trial process: a pilot study [12] , and Phase Ⅱ [13] and Phase Ⅲ clinical trials [14] .…”

Section: Introductionmentioning

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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Section: Treatment Outcomesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recurrent anal fistulae: Limited surgery supported by stem cells

García-Olmo¹,

Guadalajara²,

Rubio-Perez³

et al. 2015

WJG

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“…Of particular relevance to this study, ASCs could be considered to be safe and efficacious therapeutic tools for the treatment of Crohn's fistulae [20]. Importantly, ASCs do not cause fecal incontinence after injection into the lesion site in Crohn's disease patients with rectovaginal fistulae [19]. As such, ASCs have been granted orphan drug designation in Europe for the treatment of complex fistulae, including Crohn's fistulae.…”

Section: Introductionmentioning

confidence: 99%

“…Together with active research in the field of bone marrow-derived mesenchymal stem cells (BM-MSCs) and hematopoietic stem cells [16][17][18], autologous or allogenic adipose tissue-derived stem cells (ASCs) [14,[19][20][21][22][23] have been studied for management of Crohn's disease and other disorders. Of particular relevance to this study, ASCs could be considered to be safe and efficacious therapeutic tools for the treatment of Crohn's fistulae [20].…”

Section: Introductionmentioning

confidence: 99%

Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula

Lee¹,

Park²,

Cho³

et al. 2013

Stem Cells

251

203

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Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence. STEM

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“…Nuestro grupo de trabajo del Hospital Universitario La Paz inició en mayo del año 2002 un ensayo de factibilidad y seguridad (ensayo clínico en fase 1) sobre el uso del trasplante autólogo de células madre procedentes de la grasa en el tratamiento de la PF anorrectal en pacientes con enfermedad de Crohn, cuyos últimos resultados de seguimiento se recogieron en mayo de 2004. Se practicaron ocho procedimientos en 5 pacientes, pudiendo concluir: 1) de los lipoaspirados podemos obtener un suficiente número de cé-lulas con características citogenéticas de células madre; 2) estas células se reproducen bien en cultivo y entre 5 y 7 días se obtiene una cantidad clínicamente utilizable; 3) la inyección celular no produjo en ningún momento fenómenos de rechazo; 4) en ningún momento a lo largo del seguimiento se han detectado fenómenos de crecimiento celular incontrolado que supongan riesgo tumoral; 5) en 6 de los 8 casos tratados se logró el cierre completo (75%) y en dos hubo una clara disminución del flujo; los mayores efectos reparadores de esta terapia se han observado al cabo de 4-8 semanas de la inyección, y 6) ciertos efectos beneficiosos parecen debidos a la demostrada capacidad antiinflamatoria de estas células troncales 42,43 . A partir de estos datos de factibilidad y seguridad nos hemos planteado la posibilidad de influir sobre los procesos de cicatrización eligiendo la fístula perianal como uno de los exponentes claros del fracaso en la cicatrización.…”

Section: En Enfermedades Digestivasunclassified

Medicina regenerativa con células madre adultas

Chávarri

Pascual-Figal

Cardoso

et al. 2005

Revista Clínica Española

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En este trabajo se revisa el estado actual de la medicina regenerativa clínica con células madre de adulto en los campos cardiológico, digestivo, corneal y neurológico. Desde el punto de vista cardiológico existe experiencia clínica con progenitores de médula ósea y células de sangre periférica, así como con mioblastos esqueléticos. En el momento actual las células madre del adulto (hematopoyéticas o mesenquimales de médula ósea) constituyen la mejor opción para la regeneración del tejido cardíaco, mostrando los estudios clínicos resultados favorables, sin problemas éticos ni de seguridad. La mayoría de los estudios con mioblastos esqueléticos también han demostrado que contribuyen significativamente a mejorar la función cardíaca, sobre todo la sistólica, aunque tienen el inconveniente no aclarado totalmente, de inducir arritmias ventriculares malignas. Tanto en uno como en otro caso los estudios clínicos están en la fase inicial y se hace necesario nuevos estudios sobre todo randomizados. En el campo digestivo se presenta la experiencia pionera del Hospital La Paz del uso de células madre procedentes de la grasa abdominal en el tratamiento de la patología fistulosa de pacientes con enfermedad de Crohn. En Oftalmología el trasplante de limbo corneal es una práctica reconocida, usándose células del ojo contralateral cuando el daño es en un solo ojo y células de un donante cuando el daño es bilateral. Por último, en el campo neurológico se han identificado diversas zonas del cerebro de mamíferos adultos donde existen células troncales: el hipocampo, la zona subventricular, el bulbo olfatorio y la zona periependimaria de la médula espinal. Por otra parte, es posible obtener neuronas a partir de células troncales adultas procedentes de otros tejidos, como la médula ósea o el tejido adiposo, lo que supondría una fuente prácticamente inagotable de precursores neurales, bien mediante implante directo tras su selección o bien tras su cultivo in vitro. Aunque hasta la fecha la mayor parte de la experimentación es animal, se están poniendo ya en marcha ensayos clínicos de seguridad en esclerosis lateral amiotrófica.

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Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn's disease: a new cell-based therapy

Cited by 286 publications

References 8 publications

Recurrent anal fistulae: Limited surgery supported by stem cells

Recurrent anal fistulae: Limited surgery supported by stem cells

Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula

Medicina regenerativa con células madre adultas

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