Dataset Information

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.

ABSTRACT: : Adult human peripheral blood mononuclear cells (hPBMCs) exhibit pluripotency in vitro and so may be a valuable cell source for regenerative therapies. The efficacy of such therapies depends on the survival, differentiation, migration, and integration capacity of hPBMCs in specific tissues. In this study, we examined these capacities of transplanted hPBMCs in mouse retina as well functional improvement after transplant. We isolated hPBMCs and preinduced them for 4 days in media preconditioned with postnatal day 1 rat retina explants. Preinduction increased the proportions of hPBMCs expressing neural stem cell, neural progenitor cell, or photoreceptor markers as revealed by immunofluorescent staining, flow cytometry, and quantitative real-time polymerase chain reaction. Preinduced hPBMCs were transplanted into the subretinal space of retinal degenerative slow (RDS) and retinal degeneration 1 (RD1) mice. At 1, 3, and 6 months after transplantation, treated eyes of RDS mice were collected and cell phenotype was studied by immunofluorescent staining. Preinduced hPBMCs survived in the subretinal space; migrated away from the injection site and into multiple retinal layers; and expressed neural stem cell, neuronal, and photoreceptor markers. Finally, we assessed RD1 retinal function after subretinal transplantation and found significant improvement at 3 months after transplantation. The ease of harvesting, viability in vivo, capacity to express neuronal and photoreceptor proteins, and capacity for functional enhancement suggest that hPBMCs are potential candidates for cell replacement therapy to treat retinal degenerative diseases.

Significance

This study provides support for the use of peripheral blood mononuclear cells (PBMCs) as a potential source of pluripotent stem cells for treating retinal degeneration. First, this study demonstrated that PBMCs can differentiate into retinal neuron-like cells in vitro and in vivo. Second, some transplanted cells expressed markers for neural progenitors, mature neurons, or photoreceptors at 1, 3, and 6 months after subretinal injection. Finally, this study showed that PBMC transplantation can improve the function of a degenerated retina.

SUBMITTER: Xian B

PROVIDER: S-EPMC5070506 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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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.

Xian Bikun B Zhang Yichi Y Peng Yuting Y Huang Jianfa J Li Weihua W Wang Wencong W Zhang Min M Li Kaijing K Zhang Hening H Zhao Minglei M Liu Xing X Huang Bing B

Stem cells translational medicine 20160725 11

: Adult human peripheral blood mononuclear cells (hPBMCs) exhibit pluripotency in vitro and so may be a valuable cell source for regenerative therapies. The efficacy of such therapies depends on the survival, differentiation, migration, and integration capacity of hPBMCs in specific tissues. In this study, we examined these capacities of transplanted hPBMCs in mouse retina as well functional improvement after transplant. We isolated hPBMCs and preinduced them for 4 days in media preconditioned w ...[more]

PMID: 27458266

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Project description:BACKGROUND:Fibrinogen is a central player in the blood coagulation cascade and one of the most abundant plasma proteins. This glycoprotein also triggers important events (e.g., cell spreading, the respiratory burst and degranulation) in neutrophil cells via a ?M?2 integrin-mediated binding to the cell surface. Yet, little is known about the interaction of fibrinogen with leukocytes other than neutrophils or stimulated monocytes, although high amounts of fibrinogen protein can also be found in lymphocytes, particularly in T-cells. The aim of the present work is to unveil the dynamics and the function of fibrinogen intake in T-cells. METHODS:Using the Jurkat cell line as a T-cells model we performed fibrinogen intake/competition experiments. Moreover, by means of a targeted gene knock-down by RNA-interference, we investigated the dynamics of the intake mechanism. RESULTS:Here we show that (i) fibrinogen, although not expressed in human peripheral blood mononuclear cells, can be internalized by these cells; (ii) fibrinogen internalization curves show a hyperbolic behavior, which is affected by the presence of serum in the medium, (iii) FITC-conjugated fibrinogen is released and re-internalized by adjacent cells, (iv) the presence of human serum albumin (HSA) or immunoglobulin G (IgG), which are both protected from intracellular degradation by the interaction with the neonatal Fc receptor (FcRn), results in a decreased amount of internalized fibrinogen, and (v) FcRn-knockdown affects the dynamics of fibrinogen internalization. CONCLUSIONS:We demonstrated here for the first time that fibrinogen can be internalized and released by T-lymphocyte cells. Moreover, we showed that the presence of serum, HSA or IgG in the culture medium results in a reduction of the amount of internalized fibrinogen in these cells. Thus, we obtained experimental evidence for the expression of FcRn in T-lymphocyte cells and we propose this receptor as involved in the protection of fibrinogen from intracellular lysosomal degradation.

Dataset Information

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.

Significance

Publications

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.

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