Development of Causative Treatment Strategies for Lacrimal Gland Insufficiency by Tissue Engineering and Cell Therapy. Part 1: Regeneration of Lacrimal Gland Tissue: Can We Stimulate Lacrimal Gland Renewal In Vivo?

The incidence of cardiovascular disease (CVD) in adults are increasing worldwide with impaired repair mechanisms, leading to tissue and organ failure. With the current advancements, life expectancy has improved and has led to search for new treatment strategies that improves tissue regeneration. Recently, stem cell therapy and tissue engineering has captured the attention of clinicians, scientists, and patients as alternative treatment options. The overall clinical experience of these suggests that they can be safely used in the right clinical setting. Ultimately, large outcome trials will have to be conducted to assess their efficacy. Clinical trials have to be carefully designed and patient safety must remain the key concern. At the same time, continued basic research is required to understand the underlying mechanism of cell-based therapies and cell tissue interactions. This chapter reviews the evolving paradigm of stem cell therapy and tissue engineering approaches for clinical application and explores its implications.

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Diabetic Retinopathy and Stem Cell Therapy

10.5772/intechopen.100812 ◽

2021 ◽

Author(s):

Sevil Kestane

Keyword(s):

Stem Cells ◽

Diabetic Retinopathy ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Treatment Strategies ◽

Cell Therapies ◽

Long Time

This overview was evaluated by the development of diabetic retinopathy (DR) and the stem cell therapy approach. DR is a microvascular complication of diabetes mellitus, characterized by damage to the retinal blood vessels leading to progressive loss of vision. However, the pathophysiological mechanisms are complicated and not completely understood yet. The current treatment strategies have included medical, laser, intravitreal, and surgical approaches. It is known that the use of mesenchymal stem cells (MSC), which has a great potential, is promising for the treatment of many degenerative disorders, including the eye. In retinal degenerative diseases, MSCs were ameliorated retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Stem cell therapies show promise in neurodegenerative diseases. However, it is very important to know which type of stem cell will be used in which situations, the amount of stem cells to be applied, the method of application, and its physiological/neurophysiological effects. Therefore, it is of great importance to evaluate this subject physiologically. After stem cell application, its safety and efficacy should be followed for a long time. In the near future, widespread application of regenerative stem cell therapy may be a standard treatment in DR.

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Scaffolding Strategies for Tissue Engineering and Regenerative Medicine Applications

Materials ◽

10.3390/ma12111824 ◽

2019 ◽

Vol 12 (11) ◽

pp. 1824 ◽

Cited By ~ 48

Author(s):

Sandra Pina ◽

Viviana P. Ribeiro ◽

Catarina F. Marques ◽

F. Raquel Maia ◽

Tiago H. Silva ◽

...

Keyword(s):

Tissue Engineering ◽

Regenerative Medicine ◽

Treatment Strategies ◽

Biological Properties ◽

Inorganic Materials ◽

Bioactive Molecules ◽

Cellular Interactions ◽

Preclinical Research

During the past two decades, tissue engineering and the regenerative medicine field have invested in the regeneration and reconstruction of pathologically altered tissues, such as cartilage, bone, skin, heart valves, nerves and tendons, and many others. The 3D structured scaffolds and hydrogels alone or combined with bioactive molecules or genes and cells are able to guide the development of functional engineered tissues, and provide mechanical support during in vivo implantation. Naturally derived and synthetic polymers, bioresorbable inorganic materials, and respective hybrids, and decellularized tissue have been considered as scaffolding biomaterials, owing to their boosted structural, mechanical, and biological properties. A diversity of biomaterials, current treatment strategies, and emergent technologies used for 3D scaffolds and hydrogel processing, and the tissue-specific considerations for scaffolding for Tissue engineering (TE) purposes are herein highlighted and discussed in depth. The newest procedures focusing on the 3D behavior and multi-cellular interactions of native tissues for further use for in vitro model processing are also outlined. Completed and ongoing preclinical research trials for TE applications using scaffolds and hydrogels, challenges, and future prospects of research in the regenerative medicine field are also presented.

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Ectopic transient overexpression of OCT-4 facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells

Journal of Tissue Engineering ◽

10.1177/2041731420909208 ◽

2020 ◽

Vol 11 ◽

pp. 204173142090920

Author(s):

Seung Hyun L Kim ◽

Seunghun S Lee ◽

Inseon Kim ◽

Janet Kwon ◽

Song Kwon ◽

...

Keyword(s):

Tissue Engineering ◽

Endothelial Cells ◽

Cell Therapy ◽

Bone Morphogenetic Protein ◽

Umbilical Vein ◽

Cell Types ◽

Bone Morphogenetic Protein 4 ◽

Morphogenetic Protein ◽

Umbilical Vein Endothelial Cells

Limitation in cell sources for autologous cell therapy has been a recent focus in stem cell therapy and tissue engineering. Among various research advances, direct conversion, or transdifferentiation, is a notable and feasible strategy for the generation and acquirement of wanted cell source. So far, utilizing cell transdifferentiation technology in tissue engineering was mainly restricted at achieving single wanted cell type from diverse cell types with high efficiency. However, regeneration of a complete tissue always requires multiple cell types which poses an intrinsic complexity. In this study, enhanced osteogenic differentiation was achieved by transient ectopic expression of octamer-binding transcription factor 4 ( OCT-4) gene followed by bone morphogenetic protein 4 treatment on human umbilical vein endothelial cells. OCT-4 transfection and bone morphogenetic protein 4 treatment resulted in enhanced expression of osteogenic markers such as core-binding factor alpha 1, alkaline phosphatase, and collagen 1 compared with bone morphogenetic protein 4 treatment alone. Furthermore, we employed gelatin-heparin cryogel in cranial defect model for in vivo bone formation. Micro-computed tomography and histological analysis of in vivo samples showed that OCT-4 transfection followed by bone morphogenetic protein 4 treatment resulted in efficient transdifferentiation of endothelial cells to osteogenic cells. These results suggest that the combination of OCT-4 and bone morphogenetic protein 4 on endothelial cells would be a reliable multicellular transdifferentiation model which could be applied for bone tissue engineering.

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Isolation and Propagation of Human Corneal Stromal Keratocytes for Tissue Engineering and Cell Therapy

Cells ◽

10.3390/cells11010178 ◽

2022 ◽

Vol 11 (1) ◽

pp. 178

Author(s):

Nur Zahirah binte M. Yusoff ◽

Andri K. Riau ◽

Gary H. F. Yam ◽

Nuur Shahinda Humaira binte Halim ◽

Jodhbir S. Mehta

Keyword(s):

Tissue Engineering ◽

Cell Therapy ◽

Structural Integrity ◽

Corneal Transplantation ◽

Limiting Factor ◽

Genotypic Differences ◽

Corneal Tissue ◽

Stromal Fibroblasts ◽

Corneal Opacification

The human corneal stroma contains corneal stromal keratocytes (CSKs) that synthesize and deposit collagens and keratan sulfate proteoglycans into the stromal matrix to maintain the corneal structural integrity and transparency. In adult corneas, CSKs are quiescent and arrested in the G0 phase of the cell cycle. Following injury, some CSKs undergo apoptosis, whereas the surviving cells are activated to become stromal fibroblasts (SFs) and myofibroblasts (MyoFBs), as a natural mechanism of wound healing. The SFs and MyoFBs secrete abnormal extracellular matrix proteins, leading to corneal fibrosis and scar formation (corneal opacification). The issue is compounded by the fact that CSK transformation into SFs or MyoFBs is irreversible in vivo, which leads to chronic opacification. In this scenario, corneal transplantation is the only recourse. The application of cell therapy by replenishing CSKs, propagated in vitro, in the injured corneas has been demonstrated to be efficacious in resolving early-onset corneal opacification. However, expanding CSKs is challenging and has been the limiting factor for the application in corneal tissue engineering and cell therapy. The supplementation of serum in the culture medium promotes cell division but inevitably converts the CSKs into SFs. Similar to the in vivo conditions, the transformation is irreversible, even when the SF culture is switched to a serum-free medium. In the current article, we present a detailed protocol on the isolation and propagation of bona fide human CSKs and the morphological and genotypic differences from SFs.

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Evolving Concepts for Use of Stem Cells and Tissue Engineering for Cardiac Regeneration

Coronary and Cardiothoracic Critical Care ◽

10.4018/978-1-5225-8185-7.ch024 ◽

2019 ◽

pp. 509-543

Author(s):

Jahnavi Sarvepalli ◽

Rajalakshmi Santhakumar ◽

Rama Shanker Verma

Keyword(s):

Tissue Engineering ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Treatment Options ◽

Treatment Strategies ◽

Basic Research ◽

Underlying Mechanism ◽

Repair Mechanisms ◽

New Treatment

The incidence of cardiovascular disease (CVD) in adults are increasing worldwide with impaired repair mechanisms, leading to tissue and organ failure. With the current advancements, life expectancy has improved and has led to search for new treatment strategies that improves tissue regeneration. Recently, stem cell therapy and tissue engineering has captured the attention of clinicians, scientists, and patients as alternative treatment options. The overall clinical experience of these suggests that they can be safely used in the right clinical setting. Ultimately, large outcome trials will have to be conducted to assess their efficacy. Clinical trials have to be carefully designed and patient safety must remain the key concern. At the same time, continued basic research is required to understand the underlying mechanism of cell-based therapies and cell tissue interactions. This chapter reviews the evolving paradigm of stem cell therapy and tissue engineering approaches for clinical application and explores its implications.

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Decellularized bone extracellular matrix in skeletal tissue engineering

Biochemical Society Transactions ◽

10.1042/bst20190079 ◽

2020 ◽

Vol 48 (3) ◽

pp. 755-764

Author(s):

Benjamin B. Rothrauff ◽

Rocky S. Tuan

Keyword(s):

Tissue Engineering ◽

Bone Regeneration ◽

Tissue Regeneration ◽

Animal Studies ◽

Tumor Resection ◽

Regenerative Capacity ◽

Skeletal Tissue ◽

Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

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In vitro- / in vivo- Untersuchungen zur Biokompatibilität und Bioresorption amorpher Kieselgelfaser für das Tissue engineering humaner Knorpelgewebe

Laryngo-Rhino-Otologie ◽

10.1055/s-2004-823584 ◽

2004 ◽

Vol 83 (02) ◽

Author(s):

A Haisch ◽

A Evers ◽

K Jöhrens-Leder ◽

S Jovanovic ◽

B Sedlmaier ◽

...

Keyword(s):

Tissue Engineering

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Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

Perspectives in Surgery ◽

10.33699/pis.2019.98.9.350-355 ◽

2019 ◽

Vol 98 (9) ◽

pp. 350-355

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Therapy ◽

Portal Vein ◽

Liver Parenchyma ◽

Miniature Pig ◽

Hepatic Diseases ◽

Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

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