Delivery of Stem Cell Secretome for Therapeutic Applications

Abstract

Intensive studies on stem cell therapy reveal that benefits of stem cells attribute to the paracrine effects. Hence, direct delivery of stem cell secretome to the injured site shows the comparative therapeutic efficacy of living cells while avoiding the potential limitations. However, conventional systemic administration of stem cell secretome often leads to rapid clearance in vivo. Therefore, a variety of different biomaterials are developed for sustained and controllable delivery of stem cell secretome to improve therapeutic efficiency. In this review, we first introduce current approaches for the preparation and characterization of stem cell secretome as well as strategies to improve their therapeutic efficacy and production. The up-to-date delivery platforms are also summarized, including nanoparticles, injectable hydrogels, microneedles, and scaffold patches. Meanwhile, we discuss the underlying therapeutic mechanism of stem cell secretome for the treatment of various diseases. In the end, future opportunities and challenges are proposed.

Microneedles for in situ tissue regeneration

“…MNs can painlessly and minimally invasively penetrate a variety of tissues, including skin and cornea, without causing pain or inflammatory response [ 69 , 70 ]. Compared to conventional injections or clinical implants, MNs allow controlled delivery of the active substance to the target site with minimal tissue damage, making them more suitable for self-administration by patients.…”

“…Common events such as cervical dilatation/scraping and inflammation predispose to impaired endometrial regeneration, scar formation, fibrosis, and intrauterine adhesions (IUA) [ [145] , [146] , [147] ]. IUA is a gynecological condition in which scar tissue forms in the uterus, causing a range of symptoms, including recurrent miscarriages, amenorrhea, menorrhagia, cyclic pelvic pain, and even infertility [ 69 , 148 , 149 ]. The incidence of IUA has been reported to range from 6% to 30% in women who have undergone all types of abortions.…”

“…Ischemic cardiovascular diseases such as MI are the leading cause of death worldwide. MI is a process of adverse cardiac remodeling triggered by apoptosis and necrosis of myocardial cells, activation of inflammatory response, degradation of extracellular matrix (ECM) and tissue fibrosis following acute or chronic blockage of coronary arteries [ 69 , 155 , 156 ]. There is still no effective treatment to promote cardiac regeneration [ 157 ].…”

Cell Secretome Strategies for Controlled Drug Delivery and Wound-Healing Applications

“…Biomaterials have been a promising approach to overcome the decreased retention time of secretome components in regenerative medicine. Enhanced bioavailability is reflected in a combination of secretome and biomaterials, which leads to increased therapeutic potential [ 29 , 30 ].…”

Next generation of neurological therapeutics: Native and bioengineered extracellular vesicles derived from stem cells

“…However, with the conduct of clinical trials of stem cells, the live stem cells’ quality control in vitro and safety assessment in vivo limit its clinical application, such as the difficulties in reliable cell type characterization, precise scalable methods for cell production and purification, storage efficiency, transport stability, heterogeneity among different batches, the viability maintenance of stem cell during the infusion process, delivery and integration into the desired target tissue [12] , the tumorigenicity [13] , the immune incompatibility [14] , and ethical issues [15] associated with applications. Recent studies in neurological disease models have implied that these therapeutic effects of stem cells are due to the paracrine mechanism, especially the extracellular vesicles (EVs) [ 16 , 17 ]. These EVs from stem cells (SC-EVs) are proposed to harbor regenerative capacity to promote neurogenesis [18] and can cross the blood-brain barrier (BBB) to deliver small molecules to the CNS, which may be exploited for neurological disorders therapy.…”