Library - Crohn´s disease
Cell Transplant. 2013;22(2):279-85. doi: 10.3727/096368912X656045. Epub 2012 Sep 21.
Autologous adipose tissue-derived stem cells for the treatment of Crohn’s fistula: a phase I clinical study.
Cho YB1, Lee WY, Park KJ, Kim M, Yoo HW, Yu CS.
1Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Abstract
The present study was designed to evaluate the safety and potential of adipose tissue-derived stem cells (ASCs) for the treatment of Crohn’sfistula. In this dose escalation study, patients were sequentially enrolled into three dosing groups with at least three patients per group. The first three patients (group 1) were given 1 × 10(7) cells/ml. After 4 weeks, this dose was deemed safe, and so an additional four patients (group 2) were given 2 × 10(7) cells/ml. Four weeks later, after which this second dose was deemed safe, a third and final group of three patients were given 4 × 10(7) cells/ml. Each patient was followed for a minimum of 8 weeks. Patients who showed complete healing at week 8 were followed up for an additional 6 months. Efficacy endpoint was complete healing at week 8 after injection, defined as complete closure of the fistula track and internal and external openings without drainage or signs of inflammation. There were no grade 3 or 4 severity adverse events, and there were no adverse events related to the study drug. Two patients in group 2, treated with 2 × 10(7) ASCs/ml, showed complete healing at week 8 after injection. Of the three patients enrolled in group 3, treated with 4 × 10(7) ASCs/ml, one showed complete healing. Outcome in another patient was assessed as partial healing due to incomplete closure of the external opening, although the inside of fistula track was filled considerably and there was no drainage. All three patients with complete healing at week 8 showed a sustained effect without recurrence 8 months after injection. In conclusion, this study demonstrates the tolerability, safety, and potential efficacy of ASCs for the treatment of Crohn’s fistula and provides support for further clinical study.
Keywords: Adipose tissue-derived stem cells (ASCs); Autologous stem cells; Complete healing; Crohn’s fistula
Int J Colorectal Dis. 2013 Mar;28(3):313-23. doi: 10.1007/s00384-012-1581-9. Epub 2012 Sep 29.
Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn’s disease: results from a multicenter phase I/IIa clinical trial.
de la Portilla F1, Alba F, García-Olmo D, Herrerías JM, González FX, Galindo A.
Author information
1Coloproctology Unit, Gastrointestinal Surgery Department, Virgen del Rocio University Hospital, Avda. Manuel Siurot s/n, 41013 Seville, Spain. delaportilla@ya.com
Abstract
PURPOSE:
The management of perianal fistula in patients with Crohn’s disease is an extremely challenging medical problem as many fistulas do not respond to available treatments. The objectives were to assess the safety and efficacy of a suspension of expanded adipose-derived allogeneic mesenchymal stem cells (eASCs) for the treatment of complex perianal fistula in Crohn’s disease
METHODS:
An open-label, single-arm clinical trial was conducted at six Spanish hospitals. Twenty-four patients were administered intralesionally with 20 million eASCs in one draining fistula tract. A subsequent administration of 40 million eASCs was performed if fistula closure was incomplete at week 12. Subjects were followed until week 24 after the initial administration.
RESULTS:
Treatment-related adverse events did not indicate any clinical safety concerns after 6 months follow-up. The full analysis of efficacy data at week 24 showed 69.2 % of the patients with a reduction in the number of draining fistulas, 56.3 % of the patients achieved complete closure of the treated fistula achieved, and 30 % of the cases presenting complete closure of all existing fistula tracts. Of note, closure was strictly defined as: absence of suppuration through the external orifice and complete re-epithelization, plus absence of collections measured by magnetic resonance image scan (MRI). Furthermore, MRI Score of Severity showed statistically significant differences at week 12 with a marked reduction at week 24.
CONCLUSIONS:
Locally injected eASCs appear to be a simple, safe, and beneficial therapy for perianal fistula in Crohn’s disease patients. Additional studies are needed to further confirm the efficacy of the eASCs
Keywords: Fistulizing Crohn’s disease; Perianal fistula; Allogeneic adult stem cells
Immune Netw. 2014 Apr;14(2):81-8. doi: 10.4110/in.2014.14.2.81. Epub 2014 Apr 21.
Preclinical efficacy and mechanisms of mesenchymal stem cells in animal models of autoimmune diseases.
Lee HK1, Lim SH1, Chung IS1, Park Y1, Park MJ1, Kim JY1, Kim YG1, Hong JT1, Kim Y1, Han SB1.
Author information
1College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
Abstract
Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-β, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn’s disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.
KEYWORDS: Autoimmune diseases; Immunoregulation; Mesenchymal stem cells
Am J Reprod Immunol. 2012 Jan;67(1):1-8. doi: 10.1111/j.1600-0897.2011.01069.x. Epub 2011 Sep 23.
Immunomodulatory properties of mesenchymal stem cells: cytokines and factors.
Soleymaninejadian E1, Pramanik K, Samadian E.
1Center for Biotechnology, Institute of Science and Technology, Jawaharlal Nehru Technological University, Hyderabad, India.
Abstract
Mesenchymal stem cells (MSCs) are defined as undifferentiated cells that are capable of self renewal and differentiation into several cell types such as chondrocyte, adipocyte, osteocyte, myocyte, hepatocyte, and neuron-like cells. MSC can be isolated from bone marrow, umbilical cord blood, adipose tissue, placenta, periosteum, trabecular bone, synovium, skeletal muscle, and deciduous teeth. Immunomodulatory of MSCs is one of the important issues nowadays, because this aspect can be clinically applied for graft-versus-host and autoimmune diseases. In this review, we tried to discuss in detail about cytokines and factors such as members of the transforming growth factor superfamily (transforming growth factor-β), hepatic growth factors (HGF), prostaglandin E2 (PGE2), IL-10, indolamine 2,3-dioxygenase (IDO), nitric oxide (NO), heme oxygenase-1 (HO-1), and human leukocyte antigen-G (HLA-G) that are involved in immunomodulatory of MSCs.