Regenerative therapy for spinal cord injury using iPSC technology

Abstract

Spinal cord injury (SCI) is a devastating event that causes permanent neurologic impairments. Cell transplantation therapy using neural precursor cells (NPCs) is a promising intervention aiming to replace damaged neural tissue and restore certain functions. Because the protocol to produce human induced pluripotent stem cells (iPSCs) was first established, we have attempted to apply this technology for regenerative therapy in SCI. Our group reported beneficial effects of iPSC-derived NPC transplantation and addressed safety issues on tumorigenicity after grafting. These findings will soon be tested at the clinical trial stage, the protocol of which has already been approved by the Ministry of Health, Labour and Welfare in Japan. Current transplantation therapies treat patients at the subacute phase after injury, highlighting the need for effective treatments for chronic SCI. We recently demonstrated the modest efficacy of gamma secretase inhibitor treatment of iPSC-NPCs before transplantation at the chronic phase. However, more comprehensive strategies involving combinatory therapies are essential to enhance current spinal cord regeneration treatments.

Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation

“…A signaling pathway recently associated with human genital cancer is RANK/RANKL, which seems to participate in immune cell proliferation and tumor cell survival [ 20 , 21 ] and in chronic inflammatory conditions [ 22 ]. The binding of the ligand RANKL to the RANK receptor activates a wide range of signaling cascades, including NF-kB [ 19 ], and promotes epithelial to mesenchymal transition (EMT) [ 24 , 50 ].…”

“…In fact, the RANKL-mediated RANK activation has first been described as a pathway increasing the ability of dendritic cells (DCs) to stimulate naive T cell proliferation and enhance DCs survival [ 20 , 21 ]. Moreover, RANKL signaling is crucial for the development of various immune organs such as the thymus, lymph nodes, and bone marrow, and is also implicated in chronic inflammatory conditions of the intestine, skin, and nervous system [ 22 ]. In humans, an increased expression of RANK/RANKL has been recently demonstrated in several tumors.…”

Human engineered heart tissue transplantation in a guinea pig chronic injury model

“…Yet, congestive heart failure most often represents a chronic remodeling process that, besides a loss of cardiomyocytes, involves cardiomyocyte hypertrophy and fibrosis. Evidence from neuroscience indicates chronically injured organs represent more difficult targets for regenerative strategies 13,14 . Similarly, cardiomyocyte injection, which has repeatedly demonstrated beneficial effects in subacute injury models, resulted in smaller grafts and demonstrated no beneficial effect on LV function in chronic injury models 10,15 .…”

Stem Cell Therapies for Progressive Multiple Sclerosis

“…While iPSC-derived cells have begun to see study in other clinical contexts [e.g., iPSC-derived NSCs in spinal cord injury (Nagoshi et al, 2020) and iPSC-derived retinal pigment epithelial cells for treating age-related macular degeneration (Mandai et al, 2017)], the technology has yet to undergo trials in MS despite its potential (Fossati and Douvaras, 2014). Concerns regarding the safety of pluripotent cells sources is likely to be a key factor impeding their clinical development (Ortuño-Costela et al, 2019), although case reports of embryonic stem cell transplants in MS patients have been published (Shroff, 2016).…”