Immune recognition of syngeneic, allogeneic and xenogeneic stromal cell transplants in healthy retinas

Abstract

Background Advanced therapies using adult mesenchymal stromal cells (MSCs) for neurodegenerative diseases are not effectively translated into the clinic. The cross talk between the transplanted cells and the host tissue is something that, despite its importance, is not being systematically investigated. Methods We have compared the response of the mouse healthy retina to the intravitreal transplantation of MSCs derived from the bone marrow in four modalities: syngeneic, allogeneic, xenogeneic and allogeneic with immunosuppression using functional analysis in vivo and histology, cytometry and protein measurement post-mortem. Data were considered significant (p < 0.05) after nonparametric suitable statistical tests. Results Transplanted cells remain in the vitreous and are cleared by microglial cells a process that is quicker in allotransplants regardless of immunosuppression. All transplants cause anatomical remodelling which is more severe after xenotransplants. Xeno- and allotransplants with or without immunosuppression cause macro- and microglial activation and retinal functional impairment, being xenotransplants the most detrimental and the only ones that recruit CD45+Iba1−cells. The profile of proinflammatory cytokines changes in all transplantation settings. However, none of these changes affect the retinal ganglion cell population. Conclusions We show here a specific functional and anatomical retinal response depending on the MSC transplantation modality, an aspect that should be taken into consideration when conducting preclinical studies if we intend a more realistic translation into clinical practice.

Sub-retinal transplantation of human iPSC-derived retinal sheets: A promising approach for the treatment of macular degeneration

“…Recruitment of microglial cells (IBA1+) was frequently observed near the injection site and around the grafted area ( Fig. S10A-C ) 75 . The innate immune response observed in eyes grafted with punches from the WTC Act cell line was generally more robust compared to those from the WTC UDC cell line, with significant infiltration of macrophages and IBA1+ activated microglia within the graft ( Fig.…”

Potential therapeutic strategies for photoreceptor degeneration: the path to restore vision

“…Some evidance showed that in compare to autograft BM-MSC, the allograft or xenograft transplantation could change the retinal functionality and anatomical structures in animal model. Beside the morphological changes, microglial activation and migration to surround donor cells in allotransplantation and xenotransplantations, which was followed by CD45 + cells recruitment, the expression level of anti-inflammatory proteins was significantly lower in autograft group [ 595 ]. In addition, some individual characteristic of donor such as weight [ 596 ], age [ 597 ] and the rate of health [ 598 ] might affect the transplantation efficiency.…”

The impact of acute and chronic aerobic and resistance exercise on stem cell mobilization: A review of effects in healthy and diseased individuals across different age groups

“…Autologous therapy involves the utilization of an individual's SCs or their secretions, which presents fewer concerns regarding compatibility and immunogenicity. Allogenic therapy employs SCs from a healthy donor of the same species, which still necessitates precise evaluation to prevent immunogenic reactions [ [13] , [14] , [15] , [16] ]. In xenogeneic approaches, the donor and recipient SCs originate from different species.…”

“…In this method, the use of human SCs in animal models has garnered significant attention for assessing their performance within the animal body. However, such invasive techniques employing SCs, such as bone marrow aspiration, raise considerable concerns and challenges [ [15] , [16] , [17] ]. Another non-invasive method for utilizing bone marrow-derived SCs involves their liberation into the peripheral circulation during therapies, stimulated through pharmacological agents and physical activities.…”