Adult Human Peripheral Blood Mononuclear Cells Are Capable of Producing Neurocyte or Photoreceptor-Like Cells That Survive in Mouse Eyes After Preinduction With Neonatal Retina

Xian, Bikun; Zhang, Yichi; Peng, Yuting; Huang, Jianfa; Li, Weihua; Wang, Wencong; Zhang, Min; Li, Kaijing; Zhang, Hening; Zhao, Minglei; Liu, Xing; Huang, Bing

doi:10.5966/sctm.2015-0395

Cited by 10 publications

(12 citation statements)

References 39 publications

(43 reference statements)

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“…Analysis by paired t test confirmed significantly increased expression levels of nestin, MAP-2, beta-III tubulin, and rhodopsin on day 4 (all p < 0.05). Further, qRT-PCR results were consistent with immunofluorescence staining and flow cytometry [34]. These findings suggest that pre-induction culture can drive hPBMC differentiation toward neuronal and photoreceptor lineages.…”

Section: Changes In Hpbmcs and Neonatal Rat Retinal Cells During Pre-supporting

confidence: 77%

“…Changes in hPBMCs morphology and lineage marker expression profile during pre-induction culture with rat retinal tissue were examined by phase-contrast microscopy (Leica, Wetzlar, Germany) and qRT-PCR. The detailed methods for immunofluorescence staining and flow cytometry (Supplemental Table 2 ) can be found in our previous study [ 34 ] and Supplemental Methods .…”

Section: Methodsmentioning

confidence: 99%

“…Further, these cells can be isolated relatively easily and in large quantities, making them a promising potential source for cellbased therapy research and clinical application [26][27][28][29][30]. Human PBMCs co-cultured in vitro with neonatal rat retinas and transplanted into the subretinal space of RP model mice (rd1 mice) can survive for at least 3 months, distribute to all retinal layers, and partially restore lightevoked electrophysiological responses [31][32][33][34], thus demonstrating potential utility for RP treatment.…”

Section: Introductionmentioning

confidence: 99%

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Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice

et al. 2021

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Background Retina diseases may lead to blindness as they often afflict both eyes. Stem cell transplantation into the affected eye(s) is a promising therapeutic strategy for certain retinal diseases. Human peripheral blood mononuclear cells (hPBMCs) are a good source of stem cells, but it is unclear whether pre-induced hPBMCs can migrate from the injected eye to the contralateral eye for bilateral treatment. We examine the possibility of bilateral cell transplantation from unilateral cell injection. Methods One hundred and sixty-one 3-month-old retinal degeneration 1 (rd1) mice were divided randomly into 3 groups: an untreated group (n = 45), a control group receiving serum-free Dulbecco’s modified Eagle’s medium (DMEM) injection into the right subretina (n = 45), and a treatment group receiving injection of pre-induced hPBMCs into the right subretina (n = 71). Both eyes were examined by full-field electroretinogram (ERG), immunofluorescence, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR) at 1 and 3 months post-injection. Results At both 1 and 3 months post-injection, labeled pre-induced hPBMCs were observed in the retinal inner nuclear layer of the contralateral (left untreated) eye as well as the treated eye as evidenced by immunofluorescence staining for a human antigen. Flow cytometry of fluorescently label cells and qRT-PCR of hPBMCs genes confirmed that transplanted hPBMCs migrated from the treated to the contralateral untreated eye and remained viable for up to 3 months. Further, full-field ERG showed clear light-evoked a and b waves in both treated and untreated eyes at 3 months post-transplantation. Labeled pre-induced hPBMCs were also observed in the contralateral optic nerve but not in the blood circulation, suggesting migration via the optic chiasm. Conclusion It may be possible to treat binocular eye diseases by unilateral stem cell injection. Graphical abstract

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Section: Changes In Hpbmcs and Neonatal Rat Retinal Cells During Pre-supporting

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice

et al. 2021

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“…In addition, PBMC are an easily accessible source of different types of adult stem and progenitor cells, such as HSCs, MSCs, osteoclast precursor cells, and EPCs[ 16 ]. Due to the content of different types of adult stem cells, in a favorable microenvironment the potential to differentiate into several tissue specific cells including mature blood cells, endothelial cells, hepatocytes, cardiomyocytes, smooth muscle cells, epithelial cells, neural cells, osteoblasts, osteoclasts, and myofibroblasts has been shown[ 16 - 18 ]. Furthermore, compared to bone marrow (BM) or other multipotent cells sources, the isolation of PBMC is less invasive.…”

Section: Pbmc In Regenerationmentioning

confidence: 99%

Role of the CXCR4-SDF1-HMGB1 pathway in the directional migration of cells and regeneration of affected organs

Haque

Fareez

Fong

et al. 2020

WJSC

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In recent years, several studies have reported positive outcomes of cell-based therapies despite insufficient engraftment of transplanted cells. These findings have created a huge interest in the regenerative potential of paracrine factors released from transplanted stem or progenitor cells. Interestingly, this notion has also led scientists to question the role of proteins in the secretome produced by cells, tissues or organisms under certain conditions or at a particular time of regenerative therapy. Further studies have revealed that the secretomes derived from different cell types contain paracrine factors that could help to prevent apoptosis and induce proliferation of cells residing within the tissues of affected organs. This could also facilitate the migration of immune, progenitor and stem cells within the body to the site of inflammation. Of these different paracrine factors present within the secretome, researchers have given proper consideration to stromal cell-derived factor-1 (SDF1) that plays a vital role in tissue-specific migration of the cells needed for regeneration. Recently researchers recognized that SDF1 could facilitate site-specific migration of cells by regulating SDF1-CXCR4 and/or HMGB1-SDF1-CXCR4 pathways which is vital for tissue regeneration. Hence in this study, we have attempted to describe the role of different types of cells within the body in facilitating regeneration while emphasizing the HMGB1-SDF1-CXCR4 pathway that orchestrates the migration of cells to the site where regeneration is needed.

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“…In vivo bioluminescent luciferase imaging showed 3 weeks of good survival after xenogenous transplantation, but further histological analysis suggested at least 3 months of sustainability in vivo . Similarly, there are reports of MSC sustainability on the basis of histological analysis for 2 weeks [9], or 6 weeks [10], or even 6 months [50] after transplantation in rodents with retinal degeneration. The difference of cell sustainability in histological analysis and in vivo bioluminescence imaging may be due to the methodology.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth into Retinal Photoreceptor-Like Cells and Their Sustainability In Vivo

Xie

Zhai

et al. 2019

Stem Cells International

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Retinal degeneration is characterized by the progressive loss of photoreceptors, and stem cell therapy has become a promising strategy. Many studies have reported that mesenchymal stem cell transplantation can sustain retinal structure and prolong retinal functions based on two mechanisms. One is cell replacement, and the other is the paracrine action of stem cells. Cells from human exfoliated deciduous teeth (SHEDs) show characteristics typical of mesenchymal stem cells. They are derived from the neural crest and are a potential cellular source for neural regeneration in stem cell therapy. In this study, we explored the potential of SHEDs to be induced towards the retinal photoreceptor phenotype and to be sustainable in an animal model of retinal degeneration. A factor-cocktail protocol was used to induce SHEDs towards retinal photoreceptors for 24 days, and the characteristics of the induced cells were identified in terms of morphological changes, biomarker expression and subcellular distribution, and calcium influx. SHEDs were labeled with firefly luciferase for in vivo tracking by bioluminescent imaging and then transplanted into the subretinal space of mice. Our results showed that SHEDs successfully transdifferentiated into photoreceptor-like cells, which displayed neuron-like morphology, and expressed specific genes and proteins associated with retinal precursors, photoreceptor precursors, and mature photoreceptors. In addition, calcium influx was significantly greater in the retinal-induced than in noninduced SHEDs. In vivo tracking confirmed at least 2 weeks of good survival by bioluminescent imaging and 3 months of sustainability of SHEDs by histological analysis. We conclude that SHEDs have the potential to transdifferentiate into retinal photoreceptor-like cells in vitro and maintain good viability in vivo after transplantation into mice with a normal immune system. This demonstrates preliminary success in generating photoreceptor-like cells from SHEDs and applying SHEDs in treating retinal degeneration.

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Adult Human Peripheral Blood Mononuclear Cells Are Capable of Producing Neurocyte or Photoreceptor-Like Cells That Survive in Mouse Eyes After Preinduction With Neonatal Retina

Cited by 10 publications

References 39 publications

Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice

Migration of pre-induced human peripheral blood mononuclear cells from the transplanted to contralateral eye in mice

Role of the CXCR4-SDF1-HMGB1 pathway in the directional migration of cells and regeneration of affected organs

Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth into Retinal Photoreceptor-Like Cells and Their Sustainability In Vivo

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