Human Placental Mesenchymal Stromal Cell-Derived Exosome-Enriched Extracellular Vesicles for Chronic Liver Graft-Versus-Host Disease Volume 47- Issue 3

Amir Hossein Norooznezhad, Reza Yarani, Mehrdad Payandeh*, Zohreh Hoseinkhani, Sarah Kiani, Elham Taghizadeh, Avnesh S Thakor and Kamran Mansouri

• Kermanshah university of medical sciences, Iran

Received: November 11, 2022;   Published: November 30, 2022

*Corresponding author: Mehrdad Payandeh, Kermanshah university of medical sciences, Iran

DOI: 10.26717/BJSTR.2022.47.007491

Abstract PDF

Allogeneic peripheral blood stem cells transplantation (PBSCT) is now among the treatments for different haematological diseases and malignancies such as acute myeloid leukaemia (AML) [1,2]. Although this treatment is very advanced, graft‐versus‐host disease (GVHD) is still the most common and severe side effect. [3,4]? The cumulative incidence of chronic GVHD (cGVHD) during the first year of transplantation is as high as 43.8 ± 10% among recipients of allogeneic marrow transplantation [5]. Clinically, cGVHD involves mainly skin, lung, eye, liver and musculoskeletal system, [4, 6] in which the cutaneous type is the most prevalent and earliest exhibiting type. According to the studies, the cutaneous cGVHD is associated with an inflammatory state in which anti‐inflammatory agents are the most important treatment option [7]. Human mesenchymal stromal cells (hMSC) have been used to treat many inflammatory diseases/disorders in the clinic. A recent systematic review and meta‐analysis showed that treatment with these cells is not associated with any severe or notable side effects [8]. Exosomes are natural extracellular vesicles released by different cell types and contain proteins, lipids, and RNA. These vesicles have been known to participate in intercellular interactions and communications.

The patient was a 22-year‐old Caucasian male diagnosed with ALL years ago (April 2020). Following routine treatments and after reaching complete remission, he underwent PBSCT (one session) from an identical donor (sister). After the transplantation, he presented with acute gastrointestinal (GI) GVHD on a prophylaxis immune suppression regime, with his symptoms and signs brought under control through increasing corticosteroid and cyclosporin dosages. After a year, the liver cGVHD started, with rising in ALT, AST, BIL (TOTAL AND DIRECT) AND ALK PH, which did not good responses to cyclosporine and high‐dose corticosteroids and ATG. The exosomes‐enriched EVs were isolated from placental‐derived human mesenchymal stromal cells as has been described, and the patient received three treatments at a weekly interval (June 2021; 10 months after the transplantation). In each session, 0.5- 0.8 mg (1.9-2.6 × 1011 particles) of exosome enriched EVs were administrated in 50 ml saline (0.9%) through the right cubital vein access. The patient well tolerated the treatment, and no side‐effect was observed following the intervention. Also, no infection was noted during the treatment and follow‐up period. The changes began after the third injection, when he began to feel significant changes in his condition, the patient was evaluated more closely (15 days following the last injection), his skin has become less hyperpigmented. Also, the frequency and severeness of the pruritus and icterus decreased. The patient was followed for 5 months, and the mentioned changes remained sustained [9-15].

To our knowledge, we are reporting the second case of exosome therapy for GVHD in liver cGVHD patient, which showed clinically acceptable results for both the team and the patient. The results remained stable for 5 months with no relapse. This study only investigated the hPMSC exosome therapy due to the lack of resources. The authors suggest investigating differences among other sources of MSCs such as bone marrow for cGVHD treatment. Also, changes in the environment of the MSCs could be considered as other variables in future studies.

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