Controlled Release of Stem Cell Secretome Attenuates Inflammatory Response against Implanted Biomaterials

Abstract

Inflammatory response against implanted biomaterials impairs their functional integration and induces medical complications in the host's body. To suppress such immune responses, one approach is the administration of multiple drugs to halt inflammatory pathways. This challenges patient's adherence and can cause additional complications such as infection. Alternatively, biologics that regulate multiple inflammatory pathways are attractive agents in addressing the implants immune complications. Secretome of mesenchymal stromal cells (MSCs) is a multipotent biologic, regulating the homeostasis of lymphocytes and leukocytes. Here, it is reported that alginate microcapsules loaded with processed conditioned media (pCM-Alg) reduces the infiltration and/or expression of CD68+ macrophages likely through the controlled release of pCM. In vitro cultures revealed that alginate can dose dependently induce macrophages to secrete TNF𝜶, IL-6, IL-1𝜷, and GM-CSF. Addition of pCM to the cultures attenuates the secretion of TNF𝜶 (p = 0.023) and IL-6 (p < 0.0001) by alginate or lipopolysaccharide (LPS) stimulations. Mechanistically, pCM suppressed the Nf𝜿B pathway activation of macrophages in response to LPS (p < 0.0001) in vitro and cathepsin activity (p = 0.005) in response to alginate in vivo. These observations suggest the efficacy of using MSC-derived secretome to prevent or delay the host rejection of implants.

Human umbilical cord mesenchymal stem cell promotes angiogenesis via integrin β1/ERK1/2/HIF-1α/VEGF-A signaling pathway for off-the-shelf breast tissue engineering

“…Hence, the function of hUCMSCs in promoting rapid vascularization at an early stage is vital to the retention of fat tissue. Also, the number of CD68 + macrophages associated with the severe degree of inflammatory response [ 39 ] in the tissue engineered breast was significantly reduced after hUCMSCs transplantation. This demonstrated that hUCMSCs could significantly reduce the number of CD68 + macrophages in the compound and impeded inflammatory responses, which consequently reduced the damage of adipose tissue.…”

Optimization strategies of mesenchymal stem cell-based therapy for acute kidney injury

“…Prior to its use as a bioink, alginate has been extensively explored as a culture system and delivery vehicle for MSCs in the fields of regenerative medicine and tissue engineering [ 68 – 72 ]. Alginate also plays a significant role in the controlled release of the paracrine factors derived from MSCs [ 71 , 73 , 74 ]. However, alginate offers poor biodegradability and cell adhesive properties, which limit its potential applications [ 67 , 70 ].…”

Cell Encapsulation and 3D Bioprinting for Therapeutic Cell Transplantation

“…Various stem cell types, such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), umbilical cord-derived blood stem cells (UCBs), and adipose-derived stem cells (ADSCs), have been used for therapeutics delivery toward cancer therapy with bone marrow-derived MSCs as the most common stem cell applied in cancer therapy studies . According to studies conducted so far, MSCs or their secretome are favorable for cancer treatment in mouse models of melanoma, oral cancers, cholangiocarcinoma, glioma, bladder cancer, and blocking inflammation in general . Also, MSCs have been genetically engineered to be used for carrying therapeutics to the tumor site. − Notwithstanding, MSCs also have a pro-tumorigenic potential, as shown in some types of cancer cells.…”

“…76 According to studies conducted so far, MSCs or their secretome are favorable for cancer treatment in mouse models of melanoma, 77 oral cancers, 78 cholangiocarcinoma, 79 glioma, 80 bladder cancer, 81 and blocking inflammation in general. 82 Also, MSCs have been genetically engineered to be used for carrying therapeutics to the tumor site. 83−86 Notwithstanding, MSCs also have a pro-tumorigenic potential, as shown in some types of cancer cells.…”