Novel Application Method for Mesenchymal Stem Cell Therapy Utilizing Its Attractant-Responsive Accumulation Property

Abstract

Stem cell therapy is an emerging treatment modality for various diseases. Because mesenchymal stem cells (MSCs) are known to accumulate at the site of damage, their possible clinical application has been investigated. MSCs are usually administered using intravenous injection, but this route carries a risk of pulmonary embolism. In contrast, topical injection of MSCs reportedly has an inferior therapeutic effect. We developed a remote administration method that uses collagen gel as a scaffold and investigated the effect of this scaffold on the retention of stemness, homing ability, and therapeutic effect using a mouse tooth extraction model. After verifying the retention of stemness of MSCs isolated from the bone marrow of donor mice in the scaffold, we administered MSCs subcutaneously into the back of the recipient mice with scaffold and observed the accumulation and the acceleration of healing of the extraction socket of the maxillary first molar. The MSCs cultured with scaffold retained stemness, the MSCs injected into back skin with scaffold successfully accumulated around the extraction socket, and socket healing was significantly enhanced. In conclusion, administration of MSCs with collagen scaffold at a remote site enhanced the lesion healing without the drawbacks of currently used administration methods.

Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty

“…Local administration of MSCs targeted the injury site and produced rapid results. However, there is a risk of cell death and bleeding at the site of application [ 150 ]. The systemic administration including intraperitoneal (IP), intravascular (IV), subcutaneous (SC), and intramuscular (IM) delivery have varying cell fate and therapeutic efficacy.…”

“…On the contrary, Gonçalves et al [ 152 ] contended that the IV administration of MSCs was more effective than the IP method in the treatment of colitis as IV administration managed to stimulate a higher level of immunosuppression. However, MSCs administered through the IV route tend to become entrapped in the lungs, with only 10% of the transplanted cells reaching the site of damage [ 150 , 153 , 154 ]. Roux et al [ 155 ] stated the preference of IP over IV as to avoid the risk of pulmonary embolization which may lead to the surge of an anti-inflammatory protein known as TSG6.…”

“…Nonetheless, the research data on effects of IM administration of MSCs on the musculoskeletal system is inadequate compared to the more established IV method. Ueda et al [ 150 ] injected MSCs contained in collagen scaffold to the dorsum part of mice which considerably prolonged the retention of MSCs at the transplantation site for at least two weeks. The collagen scaffold acted as a reservoir for the exogenous MSCs and preserved the self-renewal, multipotency, and homing functions of MSCs.…”

Viral Delivery Using Scaffolds

“…), которые в определенной форме (наиболее оптимальная -микросферы) могут быть введены в виде инъекции [36,37]. Локальное введение таких материалов безопаснее и эффективнее, поскольку посредством системного введения через внутривенную инъекцию лишь 10 % от первоначальной дозы достигает органа-мишени [38,39]. Однако эти данные на сегодняшний момент подтверждены лишь для повреждений тканей сердечно-сосудистой системы, костей, хрящей и кожи, в то время как доставка скаффолдов в другие ткани и органы все еще требует изучения.…”

The good and bad sides of exosomes: pre-metastatic niche formation, cancer biomarker and therapy carriers

“…By contrast, allogenic Exo elicit lower immune response [30] . The use of MSC-derived Exo for delivery of anticancer therapy was shown to hold more promise [58] than the use of MSC themselves [59] . The fact that MSC Exo carry an aerobic metabolic ability [11] may also be taken into closer consideration.…”