Intracellular ATP Delivery Causes Rapid Tissue Regeneration Upregulation of Cytokines, Chemokines, and Stem Cells.

We have reported accelerated wound healing induced by intracellular ATP delivery in rabbits, through early massive accumulation, proliferation, and M2 polarization of macrophages. Granulation tissue started to grow within first 24 h of treatment and continued the growth till the wound cavity is completely covered. However, the mechanisms underlying this macrophage response are totally unclear because no one has ever reported this before.

Significant upregulation of U1 and U4 spliceosomal snRNAs by ATP nanoliposomes explains acceleration of wound healing, due to increased pre-mRNA processing to functional mRNA.

Delayed wound healing is one of the hallmarks of diabetic complications and certain autoimmune inflammatory diseases. Extensive wound healing studies in rabbits have indicated that the delivery of ATP encapsulated in unilamellar nanoliposomes causes rapid cell proliferation and fast tracks the wound healing process. In the current study, we explored the possible molecular mechanism underlying this response by comparing gene expression in cultured rabbit kidney cells treated with either ATP nanoliposomes (containing 1 mg Mg-ATP/ml formulation) or control nanoliposomes (containing 1 mg/ml unmetabolisable gamma-thio-ATP/ml formulation).

Macrophage Differentiation in Normal and Accelerated Wound Healing.

Chronic wounds pose considerable public health challenges and burden. Wound healing is known to require the participation of macrophages, but mechanisms remain unclear. The M1 phenotype macrophages have a known scavenger function, but they also play multiple roles in tissue repair and regeneration when they transition to an M2 phenotype.