Therapeutic Potential of Low-Dose Trypanosoma Cruzi Calreticulin in Enhancing Diabetic Wound Healing and Adipose Derived Stem Cells Fibroblastic Behavior

Calreticulin (CRT) is a vital chaperone protein that regulates cellular functions via calcium homeostasis. CRT exhibits diverse roles from intracellular to extracellular functions and can impact immune response, wound healing and more. Trypanosoma cruzi Calreticulin (TcCRT) has demonstrated superior wound-healing effects, which merits exploration of its effects in diabetic wound healing. Streptozotocin-induced diabetic rats were used to prepare Adipose-Derived Stem Cells (ADSCs) and to treat dorsal skin wounds. In-vitro, isolated rat ADSCs were characterized and induced to differentiate into osteoblasts, adipocytes and fibroblasts. In-vivo, diabetic rat wounds were treated with TcCRT at 2.5 ng/µL and 1,000 ng/µL and assessed histologically. Statistical analyses were conducted to assess the results. ADSCs cultured medium with added TcCRT exhibits fibroblastic behavior, expressing high levels of Tenascin-C (TN-C) and Matrix Metalloproteinase-1 (MMP-1) in-vitro. In-vivo, low-dose TcCRT accelerates re-epithelialization, granulation tissue formation and dermal maturation in diabetic rat wounds. We showed that low TcCRT concentrations are more effective than high doses, suggesting potential therapeutic use for chronic wounds.