Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells

Siqueira, Rubens Camargo; Voltarelli, Júlio César; Messias, André; Jorge, Rodrigo

doi:10.1590/s0004-27492010000500019

Cited by 38 publications

(47 citation statements)

References 54 publications

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“…Although the mechanisms of action of Lin − BMCs after transplantation are not fully elucidated, they may include (i) differentiation to specialized cells, for example, retinal epithelial cells or neurons, (ii) acting by paracrine or autocrine effects through the secretion of trophic factors, for example, the production of soluble mediators to promote residual cell survival, and, finally, (iii) contribution to immunomodulatory functions [19]. Several studies showed that transplanted BMCs develop morphological and phenotypic neural, glial, and epithelial markers, thus providing evidence for their differentiation into several types of neural and other retinal cells, including photoreceptors, retinal pigment epithelium, and endothelial cells [17, 20–22].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective and Antiapoptotic Activity of Lineage-Negative Bone Marrow Cells after Intravitreal Injection in a Mouse Model of Acute Retinal Injury

Machalińska

Rogińska

Pius-Sadowska

et al. 2015

Stem Cells International

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We investigated effects of bone marrow-derived, lineage-negative cell (Lin−BMC) transplantation in acute retinal injury. Lin−BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin−BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin−BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin−BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin−BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective and Antiapoptotic Activity of Lineage-Negative Bone Marrow Cells after Intravitreal Injection in a Mouse Model of Acute Retinal Injury

Machalińska

Rogińska

Pius-Sadowska

et al. 2015

Stem Cells International

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“…7 The population of adult stem cells in the BM can restore the blood ocular barrier through a paracrine effect or interfere with the osmotic gradient, favouring the absorption of the oedema fluid. 8,9 The results of this phase 2 clinical study are still being analysed, but this special case is the first report of an immediate clinical response using intravitreal auto-BMHSCT for the treatment of retinal disease and may open new horizons in the therapeutic possibilities for macular oedema. Further analysis of this trial will investigate this finding in the long term and determine whether there are correlations between this finding and other retinal functional or morphological changes related to intravitreal auto-BMHSCT for RP.…”

mentioning

confidence: 96%

Resolution of macular oedema associated with retinitis pigmentosa after intravitreal use of autologous BM-derived hematopoietic stem cell transplantation

Siqueira

Messias

Voltarelli

et al. 2012

Bone Marrow Transplant

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“…Moreover, MSC might also remodel the extracellular matrix or activate the endogenous cell by cell-cell interaction. 39 In addition, MSC have strong immunomodulatory properties against alloreactivity of T lymphocytes and dendritic cells. 40 All these paracrine actions could modulate the microenvironments and niches within the diseased retina so that the retinal neurons can be protected and repaired.…”

Section: Retinal Research On Stem Cellsmentioning

confidence: 99%

Prospects of Stem Cells for Retinal Diseases

Lam

Cheung

2013

Asia-Pacific Journal of Ophthalmology

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Retinal diseases, including glaucoma, retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration, are the leading causes of irreversible visual impairment and blindness in developed countries. Traditional and current treatment regimens are based on surgical or medical interventions to slow down the disease progression. However, the number of retinal cells would continue to diminish, and the diseases could not be completely cured. There is an emerging role of stem cells in retinal research. The stem cell therapy on retinal diseases is based on 2 theories: cell replacement therapy and neuroprotective effect. The former hypothesizes that new retinal cells could be regenerated from stem cells to substitute the damaged cells in the diseased retina, whereas the latter believes that the paracrine effects of stem cells modulate the microenvironments of the diseased retina so as to protect the retinal neurons. This article summarizes the choice of stem cells in retinal research. Moreover, the current progress of retinal research on stem cells and the clinical applications of stem cells on retinal diseases are reviewed. In addition, potential challenges and future prospects of retinal stem cell research are discussed.

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Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells

Cited by 38 publications

References 54 publications

Neuroprotective and Antiapoptotic Activity of Lineage-Negative Bone Marrow Cells after Intravitreal Injection in a Mouse Model of Acute Retinal Injury

Neuroprotective and Antiapoptotic Activity of Lineage-Negative Bone Marrow Cells after Intravitreal Injection in a Mouse Model of Acute Retinal Injury

Resolution of macular oedema associated with retinitis pigmentosa after intravitreal use of autologous BM-derived hematopoietic stem cell transplantation

Prospects of Stem Cells for Retinal Diseases

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