Adipose-Derived Stem Cells in Crohn's Rectovaginal Fistula

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

doi:10.1155/2010/961758

Cited by 76 publications

(38 citation statements)

References 9 publications

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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%

See 1 more Smart Citation

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%

“…García-Olmo et al [13] 2009 Perianal fistula with or without Crohn's disease Phase Ⅱ Autologous eASC Not specified Two arms: fibrin glue, fibrin glue + eASC García-Olmo et al [22] 2010 Recto-vaginal fistula in Crohn's disease…”

Section: Acknowledgmentsmentioning

confidence: 99%

Recurrent anal fistulae: Limited surgery supported by stem cells

García-Olmo¹,

Guadalajara²,

Rubio-Perez³

et al. 2015

WJG

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“…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

242

197

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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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“…But now, after the reported paracrine effects in several MSCs therapies we know that MSCs, far from building those tissues, they exert immunomodulatory functions, secreting, in addition, several bioactive molecules that inhibit apoptosis and scarring at sites of injury, and stimulate angiogenesis and mitosis of tissue-specific progenitors (Caplan, 2009;Ito et al, 2010;Park et al, 2010). These actions have been found either when the implanted MSCs coming from BM or adipose derived in adherent cell cultures (García-Olmo et al, 2010) or when the mononuclear fraction of BM was infused. We cannot predict the extent of the paracrine effect, immunomodulatory, or if the effective replenishment of differentiated cells can be assigned, in each case, to the MSCs, or whether these effects have some degree of integration between them.…”

Section: Resultsmentioning

confidence: 99%