Monocytes Stimulated with Conditioned Medium from Calcitriol-Treated Mesenchymal Stem Cells Exhibit Inhibition of Inflammatory Responses in Experimental Ulcerative Colitis

Ghorashi, Mahsa; Shayegh, Jalal; Esmaeili Gouvarchin Ghaleh, Hadi

doi:10.30491/jabr.2025.506447.1845

Monocytes Stimulated with Conditioned Medium from Calcitriol-Treated Mesenchymal Stem Cells Exhibit Inhibition of Inflammatory Responses in Experimental Ulcerative Colitis

Document Type : Original Article

Authors

Mahsa Ghorashi ¹

Jalal Shayegh ¹

Hadi Esmaeili Gouvarchin Ghaleh ²

¹ Faculty of Veterinary Medicine, Shab. C., Islamic Azad University, Shabestar, Iran

² Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

10.30491/jabr.2025.506447.1845

Abstract

Introduction: Mesenchymal stem cells (MSCs) are widely used to treat autoimmune and inflammatory diseases by modulating immune system activity. Several studies have shown that the administration of micronutrients such as calcitriol, which has active receptors on MSCs, can enhance the production of immunomodulatory substances. Conditioned medium (CM) derived from MSCs can induce monocytes and macrophages to initiate various anti-inflammatory pathways. This experimental study aimed to evaluate the effects of monocytes stimulated with CM from calcitriol-treated MSCs in a mouse model of ulcerative colitis (UC).
Materials and Methods: Male BALB/c mice were divided into the following groups: healthy controls (negative control), untreated UC (positive control), UC treated with untreated monocytes, UC treated with calcitriol-CM-stimulated monocytes, and UC treated with mesalazine. Following UC induction and the respective therapies, the animals were euthanized for tissue sampling. Levels of nitric oxide (NO), myeloperoxidase (MPO), and the pro-inflammatory cytokines interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), as well as intestinal tissue lesions, were assessed using biochemical and histological analyses.
Results: Our results revealed that both mesalazine and treated monocytes mitigated intestinal tissue lesions by significantly reducing MPO and NO levels and suppressing the production of the pro-inflammatory cytokines IL-1, IL-6, and TNF-α (p < 0.05).
Conclusions: Monocytes stimulated with CM from calcitriol-treated MSCs exhibit anti-inflammatory properties and promote beneficial tissue regeneration in UC. This approach may be used in conjunction with standard pharmacological treatments for UC management.

Keywords

Ulcerative Colitis

MSCs-derived Conditioned Medium

Calcitriol, Monocyte

Mesalazine