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©The Author(s) 2018.
World J Clin Cases. Oct 26, 2018; 6(12): 493-500
Published online Oct 26, 2018. doi: 10.12998/wjcc.v6.i12.493
Published online Oct 26, 2018. doi: 10.12998/wjcc.v6.i12.493
Table 1 Composite of autologous adipose tissue derived stem cell therapy trials
Author | Yerr of study | Fistula site | Type of study | Study population | Method of administration | Healing type of fistula | Safety | Outcome |
García-Olmo et al[5] | 2003 | RV | Case Report | 1 | Injection of cells into rectal mucosa | Fully healed | No AE or SAE | Complete resolution at 1 wk with closure still at 3 mo |
Lee et al[6] | 2013 | TS SS IS ES | Clinical Trial, Phase II Multi-center | 33 | Fistula tract was curetted and irrigated and then ASCs were injected into the submucosa of tract and opening | 27 of 33 patients with complete fistula healing at 8 wk 1 of 7 without complete healing had healing after 2nd dose 5 of 33 patients with > 50% closure | 60% postoperative pain 19% anal pain -7% anal bleeding 1 patient with exacerbation of disease 1 patient with peritonitis from enteritis from CD | 79% patients with complete closure after first dose |
Cho et al[7] | 2013 | TS SS ES | Clinical Trial, Phase I Multi-center | 10 | Tract curettage was performed and internal opening was closed. Then, subcutaneous adipose tissue collected by liposuction was injected into the fistula tract wall and the surrounding internal opening | Group 1: Three patients with partial closure Group 2: Two patients with complete healing Group 3: One patient with complete healing, one with partial healing | 13 AE in 7 patients which were not related to study drug: pain, diarrhea 2 patients SAE: enterocolitis, infliximab administration for new fistulas unrelated to target fistula | All patients with complete closure at 8 wk had sustained complete healing at 8 mo 50% patients after single injection with complete healing |
Cho et al[8] | 2015 | TS SS ES | Clinical Trial, Phase II Multi-center | 43 | Tract curettage was performed and internal opening was closed. Then, subcutaneous adipose tissue collected by liposuction was injected into the fistula tract wall and the surrounding internal opening. This was done on a primary endpoint of 8 wk; then a retrospective clinical study was conducted looking at patient outcomes after 2 yr | 41 of 43 patients were enrolled in the retrospective clinical study After excluded patient: 27 of 33 patients with complete closure | 53 AE in 30 patients: abdominal pain (17.1%), eczema (9.8%) exacerbation of disease (9.8%), anal inflammation (7.3%), diarrhea (7.3%), fever (7.3%) | At 12 and 24 mo, respectively, 80% (P ≤ 0.0001) and 75% (P ≤ 0.001) of patients continued to have complete closure |
Dietz et al[9] | 2017 | TS SS IS | Clinical Trial, Phase I Multi-center | 12 | Delivered ASC to the fistula through attachment of bioabsorbable matrix for surgical placement (MSC-MATRIX) through intraoperative placement | 9 of 12 patients with complete healing at 3 mo 10 of 12 patients with compete healing at 6 mo | 1 SAE from CD not study (debridement of granulation tissue of fistula tract) 2 AE: seromas at site of fat collection 11 AE: due to underlying CD | 83.3% patients at 6 mo with complete healing after MSC-MATRIX placed |
Table 2 Composite of autologous bone marrow derived stem cell therapy trials
Author | Year of study | Fistula site | Study population | Method of administration | Healing type of fistula | Safety | Outcome |
Ciccocioppo et al[10] | 2015 | Perianal Enterocutaneous | 10 | Serial intrafistula injections of autologous bone marrow MSCs | 2 patients with no recurrence of fistula at 5 yr | No adverse events | Fistula relapse free: 88% at 1 yr, 50% at 2 yr, and 37% during the following 4 yr |
Table 3 Composite of allogeneic adipose tissue derived stem cell therapy trials
Author | Year of study | Fistula site | Study population | Method of administration | Healing type of fistula (unhealed, partially, fully) | Safety | Outcome |
García-Arranz et al[11] | 2016 | RV | 10 | Tract curettage was performed and vaginal or rectal flap added with intralesional injection of 20 million allogeneic adipose stem cells injected into the fistula tract and vaginal submucosa. If complete healing was not seen at 12 wk, patients were re-administered stem cells | 2 patients with complete healing at 12 wk 2 patients with complete healing from the 8 patients with second administration of stem cells 9 patients at some point during the study had fistula healing | No SAE or AE | 3 of 5 patients included in total (others excluded during study) remained healed at 52 wk, showing 60% efficacy |
de la Portilla et al[12] | 2013 | Perianal | 24 | Intralesional fistula tract injection with stem cells with repeat administration at 12 wk with dose escalation if incomplete closure | 38.1% patients achieved complete closure at week 12 65.3% patients achieved complete closure at week 24 | 13 patients with 32 AE and of these 5 were treatment related: anal abscess (3 patients), pyrexia (1 patient), uterine leiomyoma (1 patient) | 69.2% patients had fistula reduction at 24 wk |
Panés et al[13] | 2016 | TS SS IS ES | 212 | Patient randomized into two groups: Placebo with 24 ml saline Intralesional injection of Cx601 cells Study conducted over 24 wk | 50% patients with Cx601 vs 34% placebo achieved complete fistula healing and remained closed at week 24 (P = 0.024) | TEAE: proctalgia, anal abscess, and nasopharyngitis 5% in treatment group and 6% in placebo group withdrew | Cx601 is effective and safe for treatment of refractory fistulizing CD |
Panés et al[14] | 2017 | TS SS IS ES | 212 | This was a continuation of the above study from 24 to 52 wks Patient randomized into two groups: Placebo with 24 ml saline Intralesional injection of Cx601 cells | 35%-40% patients withdrew before end of study 59.2% patients with Cx601 vs 41.6% patients with placebo (P = 0.013) achieved clinical remission 56.3% patients with Cx601 versus 38.6% patients with placebo (P = 0.010) achieved combined remission | TEAE: 76.7% in treatment group and 72.5% in control group: anal abscess/fistula 8.7% treatment group and 8.8% control group withdrew | Cx601 is safe and effective for treatment refractory complex perianal fistulas in patients with CD |
Wainstein et al[15] | 2018 | TS IS Pouch-vaginal | 9 (2 of 9 patients had 2 fistulas, so total fistula count was 11) | Two part study including: Examination under anesthesia, fistula mapping, drainage and seton placement Setons were removed 4-6 wks afterwards with ASC injected with biological plug formation | Complete healing in 10 of 11 fistulas Partial healing in 1 of 11 fistulas | No AE or SAE | Fistulizing disease can be treated successfully with a multi-approach treatment including ASCs, platelet rich plasma, and endorectal advancement flaps |
Table 4 Composite of allogeneic bone marrow derived stem cell therapy trials
Author | Year of study | Fistula site | Study population | Method of administration | Healing type of fistula (unhealed, partially, fully) | Safety | Outcome |
Molendijk et al[1] | 2015 | Perianal | 21 | Patients assigned to four groups with curettage then intralesional fistula tract injection with stem cells or placebo (1) 1 × 107 (2) 3 × 107 (3) 9 ×107 (4) placebo | Week 24 fistula healing for groups (1) 66.7% (n = 5) (2) 85.7% (n = 5) (3) 28.6% (n = 5) (4) 33.3% (n = 6) | All patients reported pain and pus and/or discharge from fistula for 1 wk postoperatively One patient in each group (1, 2, 3, and placebo) developed perianal abscess | Use of intralesional injections of 3 × 107 was successful in fistula healing. |
Table 5 Summary of all clinical trials evaluating stem cell therapy for fistulizing inflammatory bowel disease
Author | Year of study | Fistula site | Study population | Stem cell therapy | Method of administration | Healing type of fistula | Safety | Outcome |
Sanz-Baro et al[16] | 2015 | RV Perianal | 5 | 2 patients with Autologous ASC injected into fistula 3 patients with Allogeneic ASC injected into fistula | All 5 patients treated with either autologous or allogeneic ASCs and achieved remission who became pregnant were given data collection forms assessing age of treatment with ASCs, gestation age, gestational complications, any medication used during pregnancy for CD, type of delivery, fetal weight, and newborn malformations | 2 of 5 patients with gestational complications of first term abortions, fetal growth restriction, and small for gestational age 1 of 4 patients who delivered with newborn malformations of syndactyly and clinodactyly | Two of the five patients experienced gestational complications: first trimester miscarriages, fetal growth restriction, and small for gestational age | No evidence that allogeneic or autologous ASC affects fertility in women |
- Citation: Turse EP, Dailey FE, Naseer M, Partyka EK, Tahan V. One more chance of fistula healing in inflammatory bowel disease: Stem cell therapy. World J Clin Cases 2018; 6(12): 493-500
- URL: https://www.wjgnet.com/2307-8960/full/v6/i12/493.htm
- DOI: https://dx.doi.org/10.12998/wjcc.v6.i12.493