A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy

Lü, Bin; Lin, Yuan; Tsai, Yu‐Lin; Girman, Sergey; Adamus, Grażyna; Jones, Melissa K.; Shelley, Brandon; Svendsen, Clive N.; Wang, Shaomei

doi:10.1167/tvst.4.1.7

Cited by 12 publications

(30 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unlike RSCs/RPCs, NSCs/NPCs do not differentiate into mature retinal cells, and instead may aid in photoreceptor preservation by secreting neurotrophic factors and phagocytizing photoreceptor outer segment (Cuenca et al, 2013; Gamm et al, 2007; Nishida et al, 2000; Tsai et al, 2015). NSCs/NPCs can be transplanted via subretinal injection and typically do not integrate within the host photoreceptor layer, yet the cells can migrate within the subretinal space following subretinal injection to exert an effect on a larger portion of the retina (Banin et al, 2006; Lu et al, 2015; Meyer et al, 2006; Tsai et al, 2015). Each type of cell has individual benefits as a preservation strategy, but the true test will be in efficacy results following clinical trials in humans.…”

Section: Cell-based Therapeutic Strategies For Rddsmentioning

confidence: 99%

“…Conversely, the grafted cells themselves may be able to combat this by secreting factors to modulate the immune response (Baraniak and McDevitt, 2010; Jones MK et al, 2016). A majority of the clinical trials have detected minimal immune-related responses due to the cells themselves, and re-dosing studies in animals have shown that there is no adverse response to second injections while on immunosuppression (Lu et al, 2015). In the event that there is rejection, the possibility of surgically removing the graft would be difficult.…”

Section: Future Directionsmentioning

confidence: 99%

“…If there is not enough cell survival and engraftment, or if the cells die over the life of the patient, then it may be possible and necessary to inject more cells. Although RPE or supportive cells can be cultured and expanded in vitro , the cells have not been shown to be proliferative in vivo (Kanemura et al, 2014; Lu et al, 2015; Stanzel et al, 2014). While this suggests no tumorigenesis, it also indicates that cells cannot replenish themselves.…”

Section: Future Directionsmentioning

confidence: 99%

“…While this suggests no tumorigenesis, it also indicates that cells cannot replenish themselves. NPCs are well-tolerated and survive within the subretinal space for extended periods of time, and re-dosing studies have not shown immune-related responses (Lu et al, 2015); however, the feasibility of re-dosing has not been tested in clinical studies.…”

Section: Future Directionsmentioning

confidence: 99%

See 3 more Smart Citations

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

Jones

Lü

Girman

et al. 2017

Progress in Retinal and Eye Research

Self Cite

View full text Add to dashboard Cite

Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments.

show abstract

Section: Cell-based Therapeutic Strategies For Rddsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

See 2 more Smart Citations

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

Jones

Lü

Girman

et al. 2017

Progress in Retinal and Eye Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Currently, stem cell–based therapies are being tested for clinical use and offer the potential to treat a number of RDDs . One particular type of stem cell, human neural progenitor cells (hNPCs), is currently being tested for neuroprotective effects in other neurodegenerative disorders and has similarly been shown to aid in visual function and photoreceptor preservation in animal models of retinal degeneration . In animal models of retinal degeneration, hNPCs are able to phagocytize photoreceptor outer segment in vivo, exert a greater beneficial effect with expression of neurotrophic factors, and cause immunomodulatory effects on the host tissue .…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Proteomic Comparison of Human Neural Progenitor Cell‐Induced Photoreceptor Survival

et al. 2019

Self Cite

View full text Add to dashboard Cite

Retinal degenerative diseases lead to blindness with few treatments. Various cell‐based therapies are aimed to slow the progression of vision loss by preserving light‐sensing photoreceptor cells. A subretinal injection of human neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) rat model of retinal degeneration has aided in photoreceptor survival, though the mechanisms are mainly unknown. Identifying the retinal proteomic changes that occur following hNPC treatment leads to better understanding of neuroprotection. To mimic the retinal environment following hNPC injection, a co‐culture system of retinas and hNPCs is developed. Less cell death occurs in RCS retinal tissue co‐cultured with hNPCs than in retinas cultured alone, suggesting that hNPCs provide retinal protection in vitro. Comparison of ex vivo and in vivo retinas identifies nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) mediated oxidative response signaling as an hNPC‐induced pathway. This is the first study to compare proteomic changes following treatment with hNPCs in both an ex vivo and in vivo environment, further allowing the use of ex vivo modeling for mechanisms of retinal preservation. Elucidation of the protein changes in the retina following hNPC treatment may lead to the discovery of mechanisms of photoreceptor survival and its therapeutic for clinical applications.

show abstract

Structural divergence of essential triad ribbon synapse proteins among placental mammals – Implications for preclinical trials in photoreceptor transplantation therapy

Laver

Matsubara

2017

Experimental Eye Research

View full text Add to dashboard Cite

A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy

Cited by 12 publications

References 60 publications

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

In Vitro and In Vivo Proteomic Comparison of Human Neural Progenitor Cell‐Induced Photoreceptor Survival

Structural divergence of essential triad ribbon synapse proteins among placental mammals – Implications for preclinical trials in photoreceptor transplantation therapy

Contact Info

Product

Resources

About