Advanced Regenerative Medicine Strategies for Treatment of Perianal Fistula in Crohn’s Disease

Author(s):  
Hojjatollah Nazari ◽  
Vahid Yaghoubi Naei ◽  
Asieh Heirani Tabasi ◽  
Abolfazl Badripour ◽  
Reza Akbari Asbagh ◽  
...  

Abstract Regenerative medicine is an emerging therapeutic method that aims to reconstruct tissues and organs. This advanced therapeutic approach has demonstrated great potential in addressing the limitations of medical and surgical procedures for treating perineal fistula in patients with Crohn’s disease. Recent developments in stem cell technology have led to a massive good manufacturing practices (GMPs) production of various stem cells, including mesenchymal and embryonic cells, along with induction of pluripotent stem cells to repair damaged tissues in the fistula. The recent advances in separation and purification of exosomes, as biologic nanovesicles carrying anti-inflammatory and regenerative agents, have made them powerful tools to treat this inflammatory disease. Further, tremendous advances in nanotechnology, biomaterials, and scaffold fabrication methods enable tissue engineering methods to synthesize tissue-like structures to assist surgical techniques. This review focuses on advanced regenerative-based methods including stem cell therapy, exosome therapy, and tissue engineering used in the treatment of perianal fistula. Relevant in vitro and in vivo studies and the latest innovations in implementation of regenerative medicine for this disease are also separately reviewed. Additionally, current challenges regarding implementation of g stem cells, exosomes, and tissue engineering methods for bridging the gaps between laboratory findings and clinic application will be discussed.

2020 ◽  
Vol 5 (4) ◽  

Purpose: The purpose of this work was to comprehensively review literature to determine the safety and efficacy of stem cells for the treatment of Crohn’s disease and compare the effects of hematopoietic stem cells (HSCs) to that of mesenchymal stem cells (MSCs). Results: The data search included 5 animal models and clinical trials found on PubMed. The 5 studies included for HSCs and the 15 trails for MSCs found them to be a safe and effective as a treatment option (allogeneic and autologous bone marrow and adipose derived) for CD except for one multicenter randomized trial for HSC therapy. Most trials investigate the impact of stem cells specifically on perianal fistula, a common occurrence in patients with CD. Conclusion: While both HSCs and MSCs proved their safety and efficacy, MSC studies showed a greater therapeutic effect over HSCs. Adipose MSCs and Bone Marrow Derived MSCs reached similar clinical healing rates, with studies backing support for both sides. Across the board, autologous stem cell transplants proved to be safer and more effective compared to their allogeneic counterparts.


Author(s):  
Sarah El-Nakeep

Background: Crohn's disease (CD) is an autoimmune disease of the gastrointestinal tract, characterized by relapsing and remitting courses. The disease is debilitating in nature with three prominent phenotypic clinical presentations; fistulizing, stenosing, and inflammatory. Stem cells offer a new hope for CD patients with modifying the immune response and progression of the healing process. Aim: This mini-review discusses the role of stem cells in treating CD, their effectiveness as a new therapy and their current limitations faced. Methods: The author conducted a literature review on recent randomized controlled trials and cohort studies concerned with the topic in question using the following keywords (Crohn's Disease, perianal fistula, Stem cell therapy, mesenchymal stem cells, remission). Results: Clinical trials show that the stem cells are more effective in the CD associated complex perianal fistula than the CD enteritis. Till the time being, there are no standardized guidelines regarding; dose of stem cells used, number of doses administered, route of administration, type of stem cells used. Only one group of researchers proposed a standardized procedure for injecting mesenchymal stem cells in complex perianal fistula, according to their own experience in clinical trials. Moreover, mesenchymal stem cells and their related types (placental, adipose tissue, umbilical tissue, etc.) are the most safe and effective in clinical trials. Currently; the commercially available mesenchymal stem cells preparation (Darvadstrocel (Cx601)) is the only one approved by The United States Food and Drug Administration (FDA) for clinical use in refractory CD associated complex perianal fistula. Conclusions: Stem cell therapy (SCT) shows promise in; inducing remission in refractory Crohn's colitis, and perianal fistula, but further research is required before SCT could be applied to clinical practice guidelines


2012 ◽  
Vol 1 (1) ◽  
pp. 75-82
Author(s):  
Jordan Greenberg ◽  
Veronica Fortino ◽  
Daniel Pelaez ◽  
Herman S. Cheung

Author(s):  
Muhammad Shafiq ◽  
Onaza Ali ◽  
Seong-Beom Han ◽  
Dong-Hwee Kim

Stem cells have been extensively used in regenerative medicine and tissue engineering; however, they often lose their functionality because of the inflammatory microenvironment. This leads to their poor survival, retention, and engraftment at transplantation sites. Considering the rapid loss of transplanted cells due to poor cell-cell and cell-extracellular matrix (ECM) interactions during transplantation, it has been reasoned that stem cells mainly mediate reparative responses via paracrine mechanisms, including the secretion of extracellular vesicles (EVs). Ameliorating poor cell-cell and cell-ECM interactions may obviate the limitations associated with the poor retention and engraftment of transplanted cells and enable them to mediate tissue repair through the sustained and localized presentation of secreted bioactive cues. Biomaterial-mediated strategies may be leveraged to confer stem cells enhanced immunomodulatory properties, as well as better engraftment and retention at the target site. In these approaches, biomaterials have been exploited to spatiotemporally present bioactive cues to stem cell-laden platforms (e.g., aggregates, microtissues, and tissue-engineered constructs). An array of biomaterials, such as nanoparticles, hydrogels, and scaffolds, has been exploited to facilitate stem cells function at the target site. Additionally, biomaterials can be harnessed to suppress the inflammatory microenvironment to induce enhanced tissue repair. In this review, we summarize biomaterial-based platforms that impact stem cell function for better tissue repair that may have broader implications for the treatment of various diseases as well as tissue regeneration.


Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1133
Author(s):  
Marcin Włodarczyk ◽  
Katarzyna Czerwińska ◽  
Jakub Włodarczyk ◽  
Jakub Fichna ◽  
Adam Dziki ◽  
...  

Perianal fistula in patients with Crohn’s disease is an extremely challenging condition. The disease tends to reoccur, and with current treatment options, a large number of patients are left with active ailment and experience major morbidity. In recent years, hopeful results regarding local use of mesenchymal stem cells (MSCs) in perianal Crohn’s disease have been published. Although to this day there are no clear guidelines determining optimal dosage, injections frequency and culture conditions, their efficiency has proven to be much higher than conventionally used methods. According to studies, they can effectively induce as well as maintain fistula closure. This approach also avoids common side effects related to conventional surgical treatment.


2021 ◽  
Vol 21 ◽  
Author(s):  
Ali Hassanzadeh ◽  
Somayeh Shamlou ◽  
Niloufar Yousefi ◽  
Marzieh Nikoo ◽  
Javad Verdi

: Recently, genetic engineering by various strategies to stimulate gene expression in a specific and controllable mode is a speedily growing therapeutic approach. Genetic modification of human stem or progenitor cells, such as embryonic stem cells (ESCs), neural progenitor cells (NPCs), mesenchymal stem/stromal cells (MSCs), and hematopoietic stem cells (HSCs) for direct delivery of specific therapeutic molecules or genes has been evidenced as an opportune plan in the context of regenerative medicine due to their supported viability, proliferative features, and metabolic qualities. On the other hand, a large number of studies have investigated the efficacy of modified stem cells in cancer therapy using cells from various sources, disparate transfection means for gene delivery, different transfected yields, and wide variability of tumor models. Accordingly, cell-based gene therapy holds substantial aptitude for the treatment of human malignancy as it could relieve signs or even cure cancer succeeding expression of therapeutic or suicide transgene products; however, there exist inconsistent results in this regard. Herein, we deliver a brief overview of stem cell potential to use in cancer therapy and regenerative medicine and importantly discuss stem cells based gene delivery competencies to stimulate tissue repair and replacement in concomitant with their potential to use as an anti-cancer therapeutic strategy, focusing on the last two decades in vivo studies.


2020 ◽  
Vol 11 (1) ◽  
pp. 182-200
Author(s):  
Masomeh Maleki ◽  
Reza Zarezadeh ◽  
Mohammad Nouri ◽  
Aydin Raei Sadigh ◽  
Farhad Pouremamali ◽  
...  

AbstractRegenerative medicine and tissue engineering have been considered pioneer fields in the life sciences, with an ultimate goal of restoring or switching lost or impaired body parts. Graphene oxide (GO) is the product of graphene oxidation and presents a great opportunity to make substantial progress in the field of regenerative medicine; for example, it supports the possibility of creating a cellular niche for stem cells on a nanoparticle surface. GO creates a fascinating structure for regulating stem cell behavior, as it can potentially applied to the noninvasive chase of stem cells in vivo, the liberation of active biological factors from stem cell-containing delivery systems, and the intracellular delivery of factors such as growth factors, DNA, or synthetic proteins in order to modulate stem cell differentiation and proliferation. Due to the interesting physicochemical properties of GO and its possible usage in tissue engineering approaches, the present review aims to elaborate on the ways in which GO can improve current regenerative strategies. In this respect, the applicability of GO to the repair and regeneration of various tissues and organs, including cardiac muscle, skeletal muscle, and nervous, bone, cartilage, adipose, and skin tissues, is discussed.


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