Stem Cell Surgery and Growth Factors in Retinitis Pigmentosa Patients: Pilot Study after Literature Review

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Abstract

To evaluate whether grafting of autologous mesenchymal cells, adipose-derived stem cells, and platelet-rich plasma into the supracoroideal space by surgical treatment with the Limoli retinal restoration technique (LRRT) can exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and were divided based on retinal foveal thickness (FT) ≤ 190 or > 190 µm into group A-FT and group B-FT, respectively. The specific LRRT triad was grafted in a deep scleral pocket above the choroid of each eye. At 6-month follow-up, group B showed a non-significant improvement in residual close-up visus and sensitivity at microperimetry compared to group A. After an in-depth review of molecular biology studies concerning degenerative phenomena underlying the etiopathogenesis of retinitis pigmentosa (RP), it was concluded that further research is needed on tapeto-retinal degenerations, both from a clinical and molecular point of view, to obtain better functional results. In particular, it is necessary to increase the number of patients, extend observation timeframes, and treat subjects in the presence of still trophic retinal tissue to allow adequate biochemical and functional catering.

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Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ.

P Trayhurn, J H Beattie (2001)

The traditional role attributed to white adipose tissue is energy storage, fatty acids being released when fuel is required. The metabolic role of white fat is, however, complex. For example, the tissue is needed for normal glucose homeostasis and a role in inflammatory processes has been proposed. A radical change in perspective followed the discovery of leptin; this critical hormone in energy balance is produced principally by white fat, giving the tissue an endocrine function. Leptin is one of a number of proteins secreted from white adipocytes, which include angiotensinogen, adipsin, acylation-stimulating protein, adiponectin, retinol-binding protein, tumour neorosis factor a, interleukin 6, plasminogen activator inhibitor-1 and tissue factor. Some of these proteins are inflammatory cytokines, some play a role in lipid metabolism, while others are involved in vascular haemostasis or the complement system. The effects of specific proteins maybe autocrine or paracrine, or the site of action maybe distant from adipose tissue. The most recently described adipocyte secretory proteins are fasting-induced adipose factor, a fibrinogen-angiopoietin-related protein, metallothionein and resistin. Resistin is an adipose tissue-specific factor which is reported to induce insulin resistance, linking diabetes to obesity. Metallothionein is a metal-binding and stress-response protein which may have an antioxidant role. The key challenges in establishing the secretory functions of white fat are to identify the complement of secreted proteins, to establish the role of each secreted protein, and to assess the pathophysiological consequences of changes in adipocyte protein production with alterations in adiposity (obesity, fasting, cachexia). There is already considerable evidence of links between increased production of some adipocyte factors and the metabolic and cardiovascular complications of obesity. In essence, white adipose tissue is a major secretory and endocrine organ involved in a range of functions beyond simple fat storage.

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The potential of adipose stem cells in regenerative medicine.

Riitta Suuronen, Bettina Lindroos, Susanna Miettinen (2011)

Adipose stem cells (ASCs) are an attractive and abundant stem cell source with therapeutic applicability in diverse fields for the repair and regeneration of acute and chronically damaged tissues. Importantly, unlike the human bone marrow stromal/stem stem cells (BMSCs) that are present at low frequency in the bone marrow, ASCs can be retrieved in high number from either liposuction aspirates or subcutaneous adipose tissue fragments and can easily be expanded in vitro. ASCs display properties similar to that observed in BMSCs and, upon induction, undergo at least osteogenic, chondrogenic, adipogenic and neurogenic, differentiation in vitro. Furthermore, ASCs have been shown to be immunoprivileged, prevent severe graft-versus-host disease in vitro and in vivo and to be genetically stable in long-term culture. They have also proven applicability in other functions, such as providing hematopoietic support and gene transfer. Due to these characteristics, ASCs have rapidly advanced into clinical trials for treatment of a broad range of conditions. As cell therapies are becoming more frequent, clinical laboratories following good manufacturing practices are needed. At the same time as laboratory processes become more extensive, the need for control in the processing laboratory grows consequently involving a greater risk of complications and possibly adverse events for the recipient. Therefore, the safety, reproducibility and quality of the stem cells must thoroughly be examined prior to extensive use in clinical applications. In this review, some of the aspects of examination on ASCs in vitro and the utilization of ASCs in clinical studies are discussed.

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Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells.

Maria Idelson, Ruslana Alper, Alexey Obolensky … (2009)

Dysfunction and loss of retinal pigment epithelium (RPE) leads to degeneration of photoreceptors in age-related macular degeneration and subtypes of retinitis pigmentosa. Human embryonic stem cells (hESCs) may serve as an unlimited source of RPE cells for transplantation in these blinding conditions. Here we show the directed differentiation of hESCs toward an RPE fate under defined culture conditions. We demonstrate that nicotinamide promotes the differentiation of hESCs to neural and subsequently to RPE fate. In the presence of nicotinamide, factors from the TGF-beta superfamily, which presumably pattern RPE development during embryogenesis, further direct RPE differentiation. The hESC-derived pigmented cells exhibit the morphology, marker expression, and function of authentic RPE and rescue retinal structure and function after transplantation to an animal model of retinal degeneration caused by RPE dysfunction. These results are an important step toward the future use of hESCs to replenish RPE in blinding diseases.

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Journal

Journal ID (nlm-ta): Biomedicines

Journal ID (iso-abbrev): Biomedicines

Journal ID (publisher-id): biomedicines

Title: Biomedicines

Publisher: MDPI

ISSN (Electronic): 2227-9059

Publication date (Electronic): 30 November 2019

Publication date Collection: December 2019

Volume: 7

Issue: 4

Electronic Location Identifier: 94

Affiliations

[1 ]Low Vision Research Centre of Milan, p.zza Sempione 3, 20145 Milan, Italy; paololimoli@ 123456libero.it (P.G.L.); celeste.limoli@ 123456libero.it (C.L.)

[2 ]Department of Sense Organs, Faculty of Medicine and Odontology, Sapienza University of Rome, p.le A. Moro 5, 00185 Rome, Italy; enzomaria.vingolo@ 123456uniroma1.it

Author notes

[* ]Correspondence: marcella.nebbioso@ 123456uniroma1.it ; Tel.: +39-06-49975422; Fax: +39-06-49975425

Author information

Paolo Giuseppe Limoli https://orcid.org/0000-0003-4338-9274

Enzo Maria Vingolo https://orcid.org/0000-0002-8363-5866

Marcella Nebbioso https://orcid.org/0000-0002-5512-0849

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Publisher ID: biomedicines-07-00094

DOI: 10.3390/biomedicines7040094

PMC ID: 6966474

PubMed ID: 31801246

SO-VID: 97929b2c-135d-4361-a015-787f791d1d9b

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Stem Cell Surgery and Growth Factors in Retinitis Pigmentosa Patients: Pilot Study after Literature Review

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Abstract

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Stress signalling in stem cells

Most cited references 71

Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ.

The potential of adipose stem cells in regenerative medicine.

Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells.

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