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Rationale and design of the AlloFIST trial: a phase I/IIa study to evaluate dose escalation of allogeneic adipose-derived stroma/stem cells for the treatment of Crohns fistula

Por: Buscail · E. · Gilletta de Saint Joseph · C. · Lebrin · M. · Frument · I. · Gross · F. · Bournet · B. · Buscail · L. · Culetto · A. · Mokrane · F. · Delchier · M. C. · Quelven · I. · Daguzan · C. · Pugnet · G. · Duffas · J. P. · Ghouti · L. · Philis · A. · Carrere · N. · Lepage · B. · Le C
Introduction

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract distinguished by progressive bowel damage with a risk of structuring and penetrating complications. It is characterised by focal or segmental transmural inflammation that disrupts intestinal mucosal integrity and favours the development of abscesses and fistulas. Perianal fistula develops in 13%–39% of patients with CD. Their care is difficult but improves with medical and surgical treatment to preserve anal continence and avoid a maximum proctectomy. Combined treatment with seton placement and concomitant anti-TNF (infliximab, adalimumab) allows wound healing in 40%–70% of cases. The currently available treatments are not curative and fail to provide a long-term resolution. The injection of adipose stromal cells is currently being evaluated in clinical studies for repair-damaged tissues in various diseases (limb ischaemia, osteoarthritis, systemic sclerosis, etc). Immunoregulatory and anti-inflammatory properties of AdMSC (adipose-derived stroma/stem cells) are responsible for accelerating healing and represent an innovative approach for treating perianal fistulas associated with CD.

Methods and analysis

This phase I/IIa study is designed to assess the treatment of complex perianal fistulas linked with CD after failure of conventional treatment by injection of AdMSC (CellReady) into the fistula. Two doses of associated AdMSC will be tested for a dose escalation (5x107 and 10x107 cells) and injected into the wall of the fistula. Those eligible for inclusion include patients with controlled luminal CD characterised by a Harvey-Bradshaw score below or equal to eight and diagnosed on clinical, endoscopic, histological and/or radiological criteria, a colonoscopy dating back less than 1 year without ulcer in the rectum and presence of complex chronic perianal fistula with a maximum of two internal ports and three external ports. All patients must have social security insurance or equivalent social protection. The aim of this study is to determine the optimal dose corresponding to maximum efficacy 6 months after injection of cells with a treatment-related adverse event rate of 20%.

Ethics and dissemination

The EU CT number 2024-511821-75-00 was approved by the following Ethics Committee: CPP (committee for the protection of persons in French: comité de protection des personnes) Ouest 1 – Tours #2024UEMED-18 and ANSM (French Agency for the Safety of Health and Medicinal Products in French : Agence nationale de sécurité du médicament et des produits de santé) #2024-511821-75-00 (Sponsor number RC31/13/7030, protocol V2.1). The results will be disseminated through conventional scientific channels.

Trial registration number

NCT06636032.

The results will be disseminated through conventional scientific channels.

African Medicinal Plants in Cutaneous Wound Repair: A Comprehensive Analysis of the Role of Phytochemicals

ABSTRACT

Chronic and non-healing wounds are a global health issue with limited effective treatments. Wound care costs continue to rise, highlighting the need for new therapies. Medicinal plants, particularly African species, show promise for enhancing wound healing. This review analysed 93 studies and identified 37 relevant to wound healing, covering 39 plant species. Ten species were identified for their rich phytochemical content, specifically flavonoids, terpenoids, and alkaloids (plant-derived compounds). These compounds act synergistically, enhancing the wound healing process at each stage. Flavonoids reduce inflammation and support tissue turnover, while terpenoids enhance collagen production and wound closure. Alkaloids offer antimicrobial benefits and support wound contraction. Notable plants include Ageratum conyzoides and Aspilia africana (Asteraceae family); promoting haemostasis by lowering plasma fibrinogen and enhancing platelet-derived growth factors; Withania somnifera (Solanaceae); and Entada africana (Fabaceae), effectively regulating inflammation. In the proliferative phase, Ocimum gratissimum (Lamiaceae), Calendula officinalis (Asteraceae), and Centella asiatica (Apiaceae) although C. officinalis is native to Southern Europe, and C. asiatica an Asian-native; they are widely used in African traditional medicine and included here for their relevance in African wound healing practices; Justicia flava (Acanthaceae), Alternanthera sessilis (Amaranthaceae), and Acalypha indica (Euphorbiaceae); play key roles in enhancing collagen production, angiogenesis, and re-epithelialisation. This comprehensive analysis highlights the role of African medicinal plants in wound healing and their potential to improve wound care therapy.

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