The histological changes observed in radiation-induced proctitis include lesions and atrophy of the mucosa, caused by infiltration of inflammatory cells during the acute stage, as well as ischemia and fibrosis due to “swelling” of endothelial cells and development of endarteritis during the subacute and chronic stages. The deficit of the tissues’ regenerative potential after radiation therapy prioritizes the search for any approaches to the stimulation of regeneration in the radiation-affected rectum.

To date, a fairly large set of data has been accumulated on the regenerative effects of allogeneic MSC and their exosomal preparations in various diseases [15]. In our previous studies, we demonstrated the regenerative action of conditioned medium derived from allogeneic MSC in the treatment of chronic hard-to-heal wounds [16].

MSC launch immune modulation, neovascularization and are characterized by pronounced antifibrotic properties [17]. MSC affect antigen-presenting cells by altering the cytokine profiles of T-cells, NK-cells and dendritic cells from the proinflammatory phenotypes to tolerant ones. MSC have an immunosuppressive effect on dendritic cells, reducing the secretion of tumor necrosis factor-α, interferon-γ, costimulatory molecules (CD 80 and CD 86). They also act on T-cells, inhibiting differentiation and proliferation, and on T-regulatory cells to activate the secretion of transforming growth factor-β, interleukin-10 and prostaglandin E2. MSC are multipotent cells which can differentiate into neural, adipose, bone and epithelial cells, and also may migrate to damaged tissues and participate in the regeneration. MSC demonstrate low immunogenicity, low levels of the main histocompatibility complex (MHC) I and absence of MHC II and costimulatory molecules and are therefore considered adequate candidates for allogeneic cell therapy [18].

The safety and efficiency of allogeneic MSC and their derivates in the therapy of post-radiation proctitis in humans is still to be studied. However, the preclinical testing using animal models of ulcerative proctitis (including radiation-induced proctitis) has demonstrated the efficiency of both bone-marrow and adipose-derived MSC [18]. A few Phase IB/IIA studies have been conducted on the MSC treatment of the rectum affected by Crohn’s disease and ulcerative colitis. At the Cleveland Clinic (USA), 18 patients with Crohn’s disease complicated by perianal fistulae were treated, and the complete clinically and radiologically confirmed healing was observed in 15 patients (83%) [19]. A group of researchers from the Leiden University (Netherlands) published successful treatment results for 13 patients with refractory ulcerative colitis [20]. At the Luigi Sacco University Hospital, University of Milan (Italy), 3 patients with complicated refractory perianal fistulae due to Crohn’s disease were successfully treated [21]. The researchers from the Asan Medical Center (Seoul, Korea) have accumulated the largest experience, from 2014 to 2022 they treated 65 patients with Crohn’s disease-associated perianal fistulae with the closure rates of 66.2%, 73.8% and 75.4% for 1, 2 and 3 years, respectively [22].

Due to the difficulties with the regulations and production of allogeneic MSC and their derivates, adipose-derived autologous preparations, such as SVF, present a safe alternative for regenerative therapy. According to different data, they contain from 10 to 20% of MSC [23]. Our data testify that SVF contains no less than 10% of MSC, if judging from the number of CD44+ and CD90+ cells (Fig. 1S). The experience of Russian coloproctologists has demonstrated that adipose-derived autologous SVF is safe and efficient in the treatment of post-radiation lesions, including proctitis and rectovaginal fistulae [12].

The procedure we applied here implies the use of a purified cell suspension—SVF. We used the enzymatic method of SVF extraction, which is advantageous in respect to non-enzymatic approaches in the total cell yield per adipose tissue volume unit [24]. However, the practical application of the enzymatic method is possible only with the special equipment, expendables, trained laboratory personnel and conditions for timely aseptic transportation of the adipose tissue and prepared biomaterial. These limitations hinder the wide spread of this technique making it applicable only in the conditions of big clinics. The oncological safety of autologous adipose-derived bioproducts has been proven by a number of studies [25, 26] and should not be a limiting factor for the technique implementation.

In this study, the patient had a 5-month long therapy of post-radiation proctitis, complicated with hemorrhage, using the traditional protocols, which involved local and systemic administration of 5-aminosalicylic acid preparations, without any positive effect. In spite of the traditional treatment, the patient’s condition worsened. After the SVF treatment, we observed the stable remission of the clinical symptoms, and regression of the proctitis signs according to the histological study. Thus, the treatment of this patient prior to the SVF administration may be considered a rescue experiment, in which no active component was applied.