Autologous Mesenchymal Stem Cells, Applied in a Bioabsorbable Matrix, for Treatment of Perianal Fistulas in Patients With Crohn's Disease

Dietz, Allan B.; Dozois, Eric J.; Fletcher, Joel G.; Butler, Gregory J.; Radel, Darcie J.; Lightner, Amy L.; Dave, Maneesh; Friton, Jessica J.; Nair, Asha; Camilleri, Emily T.; Dudakovic, Amel; Wijnen, André J. van; Faubion, William A.

doi:10.1053/j.gastro.2017.04.001

Cited by 158 publications

(126 citation statements)

References 9 publications

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“…The tract is curetted and the plug trimmed to fit the diameter of the tract, and placed 6 weeks after the adipose tissue harvest/seton placement. A phase I trial of 12 patients has been completed, which demonstrated complete clinical and radiographic (MRI) healing in 10 out of 12 patients (83%) at 6 months 71. While this is the only trial to use a matrix, or scaffold, to deliver MSCs, the initial evidence shows potential for improved healing rates with the use of a matrix material for the theoretical prolonged local exposure of MSC.…”

Section: Future Strategies: Cell-based Therapy For Pfcdmentioning

confidence: 99%

Modern management of perianal fistulas in Crohn’s disease: future directions

Kotze

Shen

Lightner

et al. 2018

Gut

141

104

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Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.

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Section: Future Strategies: Cell-based Therapy For Pfcdmentioning

confidence: 99%

Modern management of perianal fistulas in Crohn’s disease: future directions

Kotze

Shen

Lightner

et al. 2018

Gut

141

104

View full text Add to dashboard Cite

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“…These techniques were developed based on their successful use in humans [1,14,15]. Healthy domestic white pigs (Sus scrofa domesticus) without any previous surgical procedures, weighing from 40 to 80 kg, were anesthetized with intramuscular tiletaminezolazepam (6 mg/kg) and xylazine (2 mg/kg), followed by intubation and anesthesia whereas the ventral recumbent position was used when harvesting fat from the back.…”

Section: Adipose Tissue Harvestmentioning

confidence: 99%

“…Autologous adipose-derived stem cells (AMDSCs; also termed mesenchymal stem cells [MSCs]) are easily obtained, multipotent, and versatile cells that have shown remarkable healing properties in varied clinical settings [1,2], but the development of effective clinical therapies requires rigorous in vitro and preclinical in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

Harvest and Culture of Porcine Adipose-Derived Mesenchymal Stem Cells for Autologous Transplantation

Sharma

Dietz

2020

Preprint

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Importance: Transplantation of adipose-derived (mesenchymal) stem cells (ADSCs) are currently under investigation for numerous novel regenerative cell therapies of the head, neck and periphery. Critical to the development of these techniques is the availability of large-animal models that can be used to test the safety and efficacy of these approaches in a manner that provides source material (in this case MSC) analogous to those developed in humans. Objective:To describe the surgical technique and laboratory procedures for harvesting and isolating porcine ADSCs that are functionally equivalent to human ADSCs without sacrificing the donor animal. Methods:The reagents and methods used in the porcine model described were purposefully focused to be able to be sufficiently analogous to those used in humans such that data developed using these techniques should support the use of porcine models for regulatory submissions. Results:We describe a method and confirm the activity of functionally analogous adipose derived porcine MSC. Two conditions were critical to move gain analogous performance: the cells needed to be incubated at porcine body temperature (39°C) and the cells were more sensitive to initial plating densities with plating densities of 20,000 cells/cm 2 being optimal.Discussion: This approach will allow reproducible and predictable use of an autologous large-animal model for testing AMDSC therapies. AbbreviationsADMSC, adipose-derived mesenchymal stem cell hADMSC, human adipose−derived mesenchymal stem cell MSC, mesenchymal stem cell pADMSC, porcine adipose−derived mesenchymal stem cell PBS, phosphate-buffered saline Sharma and Dietz -4-(JO)

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“…Local injection of autologous and allogeneic MSCs have shown positive results in multiple case series and randomized controlled trials compared to placebo in patients with complicated fistulizing disease, not responding to traditional therapies with immunomodulators, anti-TNF alpha agents, and local management, including surgery (23,24). A 12-patient, 6-month, phase 1 trial has shown an 83% rate of complete clinical healing and radiological evidence of response of complicated fistulas in CD patients treated with intrafistulous autologous MSCT (25). A different phase I study of four patients suffering from one or more refractory, complex CD fistulas were treated with a single intra-fistula injection of autologous MSCs.…”

Section: Mesenchymal Stem Cell Transplant (Msct) In Ibdmentioning

confidence: 99%