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Plasma-Based Gel Delivery System Might Be the Key to Success in Treating Injured Kidneys

DURHAM, N.C.  (MAY 30, 2019) - A study released today in STEM CELLS Translational Medicine is the first to demonstrate an efficient delivery system for the sustained release of human placental stem cell (HPSC)-derived conditioned medium (CM) to treat acute kidney injuries. The platelet-rich plasma-based gel system was able to deliver CM into the injured kidney, where it helped restore function and regenerate injured tissue.

“These results suggest that the delivery of HPSC-derived factors in a controlled manner may help efficiently repair the kidney after an injury,” said James Yoo, M.D., Ph.D., of the Wake Forest Institute for Regenerative Medicine and corresponding author on the study. “Using the patient’s own platelet-rich plasma for delivering the CM into them also minimizes possible side effects including rejection,” he added.

According to the World Health Organization, each year an estimated 5 to 10 million people succumb to kidney disease. Besides transplantation, current therapies revolve around dialysis — which only delays disease progression, but cannot replace other kidney functions. To address these limitations, cell-based approaches are being examined as an alternative to current therapies. Although they have shown promise in several preclinical and clinical studies, how to deliver the cells to the injured kidney remains an issue as direct injection can result in several unwanted side effects including immune rejection, pulmonary embolism and even teratoma formation.

“Recent studies show that stem cell-derived secretomes — the rich, complex set of molecules secreted from living cells — might overcome these issues,” Dr. Yoo said. “However, many growth factors undergo rapid degradation when they are injected into the body in a soluble form. The aim of our study was to develop a delivery system for HPSC secretomes that efficiently controls their release into the affected kidneys, thereby restoring kidney function,” he said.

The team, made up of colleagues from Wake Forest, focused on platelet-rich plasma (PRP) gel as the delivery vehicle. “PRP is an easily accessible autologous source rich in growth factors and has been shown to promote healing in animal models and clinical studies. It can be easily manipulated as a gel system that allows efficient encapsulation of CM components,” explained Hyung Eun Yim, M.D., Ph.D., a lead investigator on the study.

The CM used in their study, which was conducted on rats, came from human placental stem cells (HPSCs). These PSCs have the features of both embryonic and MSCs, such as noncarcinogenic property and capability to differentiate into all three embryonic germ layers. “PSCs secrete many trophic factors that are involved in anti-inflammatory and immunomodulatory activities, angiogenesis regulation, cell proliferation, anti-apoptosis and antioxidative stress,” Dr. Yim added. “Additionally, placentas are usually discarded as medical waste after birth so their use does not involve ethical issues.”

The researchers injected CM and PRP-encapsulated CM into rat kidneys. The results showed that CM delivery using the PRP gel system significantly enhanced cell proliferation and survival in the lab (in vitro) and in live animals (in vivo), too. Overall, it minimized renal tissue damage, leading to a faster recovery compared to saline, CM or vehicle-only injection groups.

“These results suggest that controlled delivery of HPSC-derived trophic factors may provide efficient repair of renal tissue injury,” Dr. Yoo said.

“Acute kidney injury is an ever growing problem in the clinic leading to leading to high mortality of hospitalized patients. Methods that combat this disease are not available and are highly warranted.” Professor Benjamin Dekel, one of the editors of STEM CELLS Translational Medicine commented, “Yoo and colleagues show pre-clinical data in animal models of acute kidney injury whereby a cocktail of potent molecules derived from placental stem cells and put into culture media can be delivered into injured kidneys and provide in turn a healing regenerative effect. These data open vistas to future studies utilizing factors derived from stem cells to fix kidneys and by themselves push for similar methodologies to be translated to the bedside.”

The full article, “Controlled Delivery of Stem Cell‐Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia‐Reperfusion Injury in Rats,” can be accessed at:

About STEM CELLS Translational Medicine: STEM CELLS Translational Medicine (SCTM), co-published by AlphaMed Press and Wiley, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices. SCTM is the official journal partner of Regenerative Medicine Foundation.

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