Acute kidney injury (AKI) is an independent risk factor for end-stage renal disease (ESRD) and death and is characterized by a sudden failure of renal function. The standard approach to treat AKI is mostly supportive in nature. Stem cell therapy is a promising approach in regenerative medicine and has shown to work through multiple mechanisms to effect tissue repair. Mesenchymal stem cells (MSC) are multipotent cells having angiogenic and immunomodulatory properties. They exert their therapeutic effects through paracrine action, commonly referred to as ‘secretome’. MSC release soluble factors that stimulate regeneration through pro-survival, mitogenic, anti-inflammatory, and angiogenic effects.
We induced AKI in mice by administering Cisplatin. The Cisplatin-induced AKI mice were separated in 4 groups: (1) Control group (no treatment), (2) subcapsular implantation of MSC on the kidney, (3) secretome injection along with subcapsular implantation of MSC on the kidney, (4) secretome injection alone. Mice were euthanized after 2 weeks, and blood and kidney tissues were collected for analysis.
We observed that there was an average drop in creatinine of 43% in mice that were treated with MSC alone and an average drop in creatinine of 50% in mice treated with MSC along with secretome. Treatment of mice with secretome alone proved to be toxic as these mice died after administration of secretome. Histological evaluation of kidney tissue demonstrated that cisplatin induced a significant increase in indices of kidney injury, such as glomerular casts, tubular casts, and fibrosis. A significant reduction in these indices were observed in mice that were treated with MSC and secretome ranging from minimal to no microscopic evidence of AKI. Mice treated with MSC alone displayed mild severity of AKI whereas moderated severity of AKI was seen in mice treated with secretome alone.
Our results demonstrate that MSC and secretome play a role in ameliorating the damage caused by Cisplatin-induced AKI. MSC therapy can thus augment the unmet need for therapies that promote repair and regeneration of damaged kidneys and restore kidney function."