Protective effects of mesenchymal stromal cell-derived secretome on dermonecrosis induced in rabbits by Loxosceles intermedia spider venom

Abstract

Background: Loxoscelism refers to a set of clinical manifestations caused by the bite of spiders from the Loxosceles genus. The classic clinical symptoms are characterized by an intense inflammatory reaction at the bite site followed by local necrosis and can be classified as cutaneous loxoscelism. This cutaneous form presents difficult healing, and the proposed treatments are not specific or effective. This study aimed to evaluate the protective effect of mesenchymal stromal cells-derived secretome on dermonecrosis induced by Loxosceles intermedia spider venom in rabbits. Methods: Sixteen rabbits were distributed into four groups (n = 4). Except for group 1 (G1), which received only PBS, the other three groups (G2, G3, and G4) were initially challenged with 10 μg of L. intermedia venom, diluted in 100 μL of NaCl 0.9%, by intradermic injection in the interscapular region. Thirty minutes after the challenge all groups were treated with secretome, except for group 2. Group 1 (G1-control group) received intradermal injection (ID) of 60 μg of secretome in 0.15 M PBS; Group 2 (G2) received 0.9% NaCl via ID; Group 3 (G3) received 60 μg of secretome, via ID and Group 4 (G4), received 60 μg of secretome by intravenous route. Rabbits were evaluated daily

The Hidden Power of the Secretome: Therapeutic Potential on Wound Healing and Cell-Free Regenerative Medicine—A Systematic Review

“…Additionally, advancements in production methods have enabled the development of enriched secretomes that promote healing without leaving visible scars [ 38 ]. Furthermore, the incorporation of these secretomes into innovative hydrogels and dressings has improved their effectiveness in treating chronic wounds and dermonecrosis models [ 39 , 40 ]. The secretome of bone marrow-derived MSCs has also been explored as an effective source for treating difficult wounds.…”

“…In clinical terms, the development of ready-to-use formulations has been key in the translation of secretome to regenerative medicine. Recent studies have shown that secretome-enriched gels (10% SM-hUCMSC gel) are effective in the treatment of chronic ulcers and diabetic wounds, highlighting the importance of their standardization to ensure reproducibility and efficacy [ 24 , 32 , 34 , 37 , 40 , 56 ]. Furthermore, the combination of secretome with biomaterials such as hyaluronic acid hydrogels has shown promising results in regenerative therapies [ 57 , 58 ].…”

“…Conversely, the impact of additives in the medium also affects secretome production. Research has shown that certain factors, like glucose and specific amino acids, can promote the secretion of proteins related to wound healing, thereby creating new opportunities for clinical applications in regenerative medicine and tissue repair [ 32 , 40 ].…”

The Hidden Power of the Secretome: Therapeutic Potential on Wound Healing and Cell-Free Regenerative Medicine—A Systematic Review

“…Additionally, advancements in production methods have enabled the development of enriched secretomes that promote healing without leaving visible scars [ 38 ]. Furthermore, the incorporation of these secretomes into innovative hydrogels and dressings has improved their effectiveness in treating chronic wounds and dermonecrosis models [ 39 , 40 ]. The secretome of bone marrow-derived MSCs has also been explored as an effective source for treating difficult wounds.…”

“…In clinical terms, the development of ready-to-use formulations has been key in the translation of secretome to regenerative medicine. Recent studies have shown that secretome-enriched gels (10% SM-hUCMSC gel) are effective in the treatment of chronic ulcers and diabetic wounds, highlighting the importance of their standardization to ensure reproducibility and efficacy [ 24 , 32 , 34 , 37 , 40 , 56 ]. Furthermore, the combination of secretome with biomaterials such as hyaluronic acid hydrogels has shown promising results in regenerative therapies [ 57 , 58 ].…”

“…Conversely, the impact of additives in the medium also affects secretome production. Research has shown that certain factors, like glucose and specific amino acids, can promote the secretion of proteins related to wound healing, thereby creating new opportunities for clinical applications in regenerative medicine and tissue repair [ 32 , 40 ].…”

The Hidden Power of the Secretome: Therapeutic Potential on Wound Healing and Cell-Free Regenerative Medicine—A Systematic Review

“…Additionally, advancements in production methods have enabled the development of enriched secretomes that promote healing without leaving visible scars [ 38 ]. Furthermore, the incorporation of these secretomes into innovative hydrogels and dressings has improved their effectiveness in treating chronic wounds and dermonecrosis models [ 39 , 40 ]. The secretome of bone marrow-derived MSCs has also been explored as an effective source for treating difficult wounds.…”

“…In clinical terms, the development of ready-to-use formulations has been key in the translation of secretome to regenerative medicine. Recent studies have shown that secretome-enriched gels (10% SM-hUCMSC gel) are effective in the treatment of chronic ulcers and diabetic wounds, highlighting the importance of their standardization to ensure reproducibility and efficacy [ 24 , 32 , 34 , 37 , 40 , 56 ]. Furthermore, the combination of secretome with biomaterials such as hyaluronic acid hydrogels has shown promising results in regenerative therapies [ 57 , 58 ].…”

“…Conversely, the impact of additives in the medium also affects secretome production. Research has shown that certain factors, like glucose and specific amino acids, can promote the secretion of proteins related to wound healing, thereby creating new opportunities for clinical applications in regenerative medicine and tissue repair [ 32 , 40 ].…”

The Hidden Power of the Secretome: Therapeutic Potential on Wound Healing and Cell-Free Regenerative Medicine—A Systematic Review

“…Additionally, advancements in production methods have enabled the development of enriched secretomes that promote healing without leaving visible scars [ 38 ]. Furthermore, the incorporation of these secretomes into innovative hydrogels and dressings has improved their effectiveness in treating chronic wounds and dermonecrosis models [ 39 , 40 ]. The secretome of bone marrow-derived MSCs has also been explored as an effective source for treating difficult wounds.…”

“…In clinical terms, the development of ready-to-use formulations has been key in the translation of secretome to regenerative medicine. Recent studies have shown that secretome-enriched gels (10% SM-hUCMSC gel) are effective in the treatment of chronic ulcers and diabetic wounds, highlighting the importance of their standardization to ensure reproducibility and efficacy [ 24 , 32 , 34 , 37 , 40 , 56 ]. Furthermore, the combination of secretome with biomaterials such as hyaluronic acid hydrogels has shown promising results in regenerative therapies [ 57 , 58 ].…”

“…Conversely, the impact of additives in the medium also affects secretome production. Research has shown that certain factors, like glucose and specific amino acids, can promote the secretion of proteins related to wound healing, thereby creating new opportunities for clinical applications in regenerative medicine and tissue repair [ 32 , 40 ].…”