Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy

Abstract

The use of allogeneic adipose-derived mesenchymal stromal cells (alloADSCs) represents an attractive approach for treating myocardial infarction (MI). Furthermore, adding a natural support improves alloADSCs engraftment and survival in heart tissues, leading to a greater therapeutic effect. We aimed to examine the safety and immunological reaction induced by epicardial implantation of a clinical-grade collagen scaffold (CS) seeded with alloADSCs for its future application in humans. Thus, cellularized scaffolds were myocardially or subcutaneously implanted in immunosuppressed rodent models. The toxicological parameters were not significantly altered, and tumor formation was not found over the short or long term. Furthermore, biodistribution analyses in the infarcted immunocompetent rats displayed cell engraftment in the myocardium but no migration to other organs. The immunogenicity of alloADSC-CS was also evaluated in a preclinical porcine model of chronic MI; no significant humoral or cellular alloreactive responses were found. Moreover, CS cellularized with human ADSCs cocultured with human allogeneic immune cells produced no alloreactive response. Interestingly, alloADSC-CS significantly inhibited lymphocyte responses, confirming its immunomodulatory action. Thus, alloADSC-CS is likely safe and does not elicit any alloreactive immunological response in the host. Moreover, it exerts an immunomodulatory action, which supports its translation to a clinical setting.

A Versatile Intestine‐on‐Chip System for Deciphering the Immunopathogenesis of Inflammatory Bowel Disease

“…[ 76 ] The proximity of ILCs to the IEB enables them to sense microbial endotoxin or tissue damage at an early stage and to produce IFN‐γ to recruit other innate immune cells, such as MNPs. [ 38, 77, 78 ] IFN‐γ is also an important cytokine for immune responses by CD4 + cells [ 76 ] and has been shown to drive excessive immune responses against microbial components within the apical content in IBD. [ 77 ]…”

“…[76] The proximity of ILCs to the IEB enables them to sense microbial endotoxin or tissue damage at an early stage and to produce IFN-𝛾 to recruit other innate immune cells, such as MNPs. [38,77,78] IFN-𝛾 is also an important cytokine for immune responses by CD4 + cells [76] and has been shown to drive excessive immune responses against microbial components within the apical content in IBD. [77] As an increased release of TNF-𝛼 is one of the hallmarks of intestinal inflammation, we used an anti-TNF-𝛼 therapeutic antibody -Infliximab -to demonstrate testing of anti-inflammatory therapies with our chip system.…”

“…This bioresponsive membrane allows for robust cell-cell and cell-matrix interactions and supports cellular growth and differentiation. [36][37][38] Each on-chip IEB model features multiple spatially separated basal compartments, in which different immune cell types or cytokine stimuli can be independently added or applied. Shear stress was realized through liquid flow by gravity-driven perfusion, making chip usage and operation scalable and user-friendly.…”

Exosomes from adipose-derived stem cells regulate M1/M2 macrophage phenotypic polarization to promote bone healing via miR-451a/MIF

“…Adipose-derived mesenchymal stem cells (ADSCs) are commonly used in BTE, besides they can differentiate into a variety of cell types to improve the functional recovery of different types of damaged tissues [ 22 – 25 ], their immune regulation has attracted increasing attention. These cells play therapeutic roles in many immune diseases by secreting anti-inflammatory cytokines and growth factors that counteract inflammatory factors and can effectively regulate the immune response caused by biomaterial implantation [ 26 – 28 ]. ADSCs are easy to obtain through minimally invasive surgery, with the advantages of high yield, low invasion and high proliferation rate; thus, they are considered to have excellent prospects for future clinical applications [ 29 , 30 ].…”

Advanced Progress in the Role of Adipose-Derived Mesenchymal Stromal/Stem Cells in the Application of Central Nervous System Disorders

“…Adipose-derived stem cells (ADMSCs) hold great promise for regenerative therapy, attributed to their subcutaneous Pharmaceutics 2023, 15, 2637 2 of 23 accessibility, abundance, and less invasive procurement techniques [9]. Ongoing studies exploring the application of ADMSCs in regenerative therapy stem from its promising potential [10][11][12][13]. In addition to differentiation, like other MSCs, ADMSCs promote wound healing and tissue repair mainly based on paracrine, which modulates the microenvironment comprehensively by secreting a large number of bioactive factors [14].…”