A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru

Vellore, India

A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru

Vellore, India

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Prakash Parthiban S.,Dankook University | Rana D.,A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Jabbari E.,University of South Carolina | Benkirane-Jessel N.,University of Strasbourg | And 2 more authors.
Acta Biomaterialia | Year: 2017

Clinically usable tissue-engineered constructs are currently limited due to their inability of forming microvascular networks necessary for adequate cellular oxygen and nutrient supply upon implantation. The aim of this study is to investigate the conditions necessary for microvascularization in a tissue-engineered construct using vascular endothelial growth factor (VEGF). The construct was made of gelatin methacrylate (GelMA) based cell-laden hydrogel system, which was then covalently linked with VEGF-mimicking peptide (AcQK), using human umbilical vein endothelial cells (HUVECs) as the model cell. The results of the mechanics and gene expression analysis indicated significant changes in mechanical properties and upregulation of vascular-specific genes. The major finding of this study is that the increased expression of vascular-specific genes could be achieved by employing AcQK in the GelMA based hydrogel system, leading to accelerated microvascularization. We conclude that GelMA with covalently-linked angiogenic peptide is a useful tissue engineered construct suitable for microvascularization. Statement of Significance: (1) This study reports the conditions necessary for microvascularization in a tissue-engineered construct using vascular endothelial growth factor (VEGF). (2) The construct was made of gelatin methacrylate based cell-laden hydrogel system. (3) There is a significant change observed in mechanical properties and upregulation of vascular-specific genes, in particular CD34, when AcQK is used. (4) The major finding of this study is that the increased expression of vascular-specific genes, i.e., CD34 could be achieved by employing AcQK in the GelMA based hydrogel system, leading to accelerated microvascularization. © 2017 Acta Materialia Inc.


Rana D.,A unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Ramalingam M.,A unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Ramalingam M.,Tohoku University
Materials Science and Engineering C | Year: 2017

Stem cell plays a significant role in tissue engineering and regenerative medicine. However, one of the major limitations in translation of stem cell technologies for clinical applications is limited cell survival and growth upon implantation. To address this limitation, authors have made an attempt to design polyacrylamide/alginate (PAAm/Algi) based tough hydrogel substrates and studied their impact on the survival and proliferation of human bone marrow-derived mesenchymal stem cells (hBMSCs). The PAAm/Algi hydrogel substrates have been prepared by initiator-induced free radical polymerization with mechanical properties quite similar to human soft tissues. To evaluate the efficacy of hydrogel substrates in support of cellular functions, hBMSCs were cultured on the PAAm/Algi hydrogel substrate (Gel system) and conventional tissue culture plate (TcP system) under defined conditions. The results of this study demonstrated that the cells cultured on the Gel and TcP systems showed 80–90% of cell viability throughout the period of study. The cells cultured on the Gel system showed 25% increase in proliferation after 7 days of culture, whereas the TcP system showed only an increase of 10%. These results confirm the cellular compatibility and enhanced cell proliferative nature of the hydrogel substrates, due the fact that the hydrogel substrates provided necessary microenvironmental cues to the cells as compared the conventional TcP system. The overall results suggest that the PAAm/Algi based hydrogels could be used as a potential substrate for hBMSCs culture and expansion. © 2017 Elsevier B.V.


Rana D.,Amity University | Kumar T.S.S.,Indian Institute of Technology Madras | Ramalingam M.,A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Ramalingam M.,Tohoku University
Journal of Biomaterials and Tissue Engineering | Year: 2014

This article reviews cell-laden hydrogels focusing on their impact and recent trends in tissue engineering. Tissue engineering aims to develop functionalized tissues and organs for repair and regeneration of defective body parts with help of cells and engineered matrices called scaffold. Scaffold plays a key role in tissue engineering as a supporting system to accommodate cell attachment, proliferation, migration and differentiation into a specific tissue. Scaffolds in the form of hydrogels are widely used as a support system for engineering tissues owing to their functional properties such as biocompatibility, matching physical, mechanical and chemical properties to the native niche, providing microenvironment for cells to grow and infiltrate into three-dimensional (3D) space and for providing adequate nutrient and oxygen supplies. To optimize the scaffold properties and its compatibility with native niche, cell-laden hydrogel is an appealing option that helps engineering potential tissue constructs with biomimetic structure and function. In this article, therefore, we review cell-laden hydrogels and their applications in tissue engineering with special emphasis on different types of gel scaffolds and their functional properties. Recent trends in hydrogel-based scaffolding systems, especially stem cell-laden hydrogels, gradient hydrogels, and their potential in engineering cells and tissues are also discussed. The review is expected to be useful for readers to gain an in-sight on the cell-laden hydrogel as a promising scaffolding system for tissue engineering applications such as bone, cartilage, cardiac and neural. © 2014 American Scientific Publishers.


Varadarajan N.,National Institute of Technology Rourkela | Balu R.,Indian Institute of Technology Madras | Sampath Kumar T.S.,Indian Institute of Technology Madras | Rana D.,A unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | And 3 more authors.
Journal of Biomaterials and Tissue Engineering | Year: 2014

Calcium deficient hydroxyapatite (CDHA) nanoparticles with a Ca/P ratio of 1.6 were synthesized by accelerated sonochemical process. The synthesis was carried out using calcium nitrate and diammonium hydrogen phosphate in an ultrasonic bath operated at a fixed frequency of 135 kHz and 250 Watts power. The effect of ultrasonic radiation as a function of time over the formation and structure of nanoparticles were investigated using X-ray diffraction, spectroscopy and microscopy methods. The synthesized nanocrystals showed X-ray powder diffraction pattern corresponding to that of hydroxyapatite stoichiometry with CDHA characteristics. HPO2- 4 Fourier transform infrared vibration band observed at 875 cm-1. Transmission electron microscopic analysis confirmed the nanocrystalline nature and growth of acicular, rod and needle-like CDHA nanocrystals morphology with increasing irradiation time. © 2014 American Scientific Publishers. All rights reserved.


Rana D.,A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Ramasamy K.,A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Leena M.,Karunya University | Jimenez C.,University of Los Andes, Chile | And 5 more authors.
Biotechnology Progress | Year: 2016

Stem cell-based approaches offer great application potential in tissue engineering and regenerative medicine owing to their ability of sensing the microenvironment and respond accordingly (dynamic behavior). Recently, the combination of nanobiomaterials with stem cells has paved a great way for further exploration. Nanobiomaterials with engineered surfaces could mimic the native microenvironment to which the seeded stem cells could adhere and migrate. Surface functionalized nanobiomaterial-based scaffolds could then be used to regulate or control the cellular functions to culture stem cells and regenerate damaged tissues or organs. Therefore, controlling the interactions between nanobiomaterials and stem cells is a critical factor. However, surface functionalization or modification techniques has provided an alternative approach for tailoring the nanobiomaterials surface in accordance to the physiological surrounding of a living cells; thereby, enhancing the structural and functional properties of the engineered tissues and organs. Currently, there are a variety of methods and technologies available to modify the surface of biomaterials according to the specific cell or tissue properties to be regenerated. This review highlights the trends in surface modification techniques for nanobiomaterials and the biological relevance in stem cell-based tissue engineering and regenerative medicine. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:554–567, 2016. © 2016 American Institute of Chemical Engineers


Trzeciak T.,Poznan University of Medical Sciences | Rybka J.D.,Adam Mickiewicz University | Richter M.,Poznan University of Medical Sciences | Kaczmarczyk J.,Poznan University of Medical Sciences | And 5 more authors.
Journal of Nanoscience and Nanotechnology | Year: 2016

Over the last decade the interest in the technology of tissue engineering (TE) has grown enormously, especially with respect to reparative techniques. New methods and therapeutic tools have been designed; various cell types used and novel drugs and growth factors applied for the repair of lesions in numerous tissues, in particular bone and cartilage, resulting from injuries or degenerative changes due to aging of the population. The TE requires the application of various methods, including sophisticated surgical procedures supported by techniques of cell biology and biotechnology. The latter techniques are required for choosing appropriate cell types for transplantation, elaborating optimal cell culture conditions, designing scaffolds for cell delivery, affixing temporary implantable devices in the lesion site and supplying drugs and growth factors. In the present review we describe and discuss various TE techniques used in bone and cartilage repair including: recently applied principal cell sources, and the application of nanotube-based scaffolds in the regeneration of joint cartilage. Copyright © 2016 American Scientific Publishers. All rights reserved. Printed in the United States of America.


Rana D.,A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Tabasum A.,A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Ramalingam M.,A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Ramalingam M.,Tohoku University
RSC Advances | Year: 2016

Stem cell based therapies employ engraftment or systemic administration methods for the delivery of stem cells into the target tissues to enhance their regenerative potential. However, majority of the stem cells were found to migrate away from the target site soon after the transplantation, which directly hinders their clinical efficacy, in particular while treating cartilage defects. Therefore, the present study was designed to explore the feasibility and efficacy of an alginate/polyacrylamide (Algi/PAAm) composite biomaterial in the form of cell-laden hydrogel beads as a suitable carrier system to be able to hold the stem cells at the target site and deliver them efficiently. Human bone marrow-derived mesenchymal stem cells (hBMSCs) have been used as a model cell. The beads prepared at an optimized concentration ratio were characterized to study their physicochemical properties. Furthermore, cell-encapsulated Algi/PAAm beads were evaluated for their biological properties. The result of this study has demonstrated that the Algi/PAAm beads with their optimal composition were able to maintain the viability of the encapsulated cells during the period of study, suggesting the cellular compatibility of the beads. Additionally, the encapsulated cells showed round morphology within the beads, in contrast to the 2D-cultured spindle-like shape of hBMSCs. Based on the experimental data obtained in this study, cell-laden Algi/PAAm beads may serve as a potential carrier system for stem cell delivery. © The Royal Society of Chemistry 2016.


Ramalingam M.,A unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Ramalingam M.,Tohoku University | Rana D.,A unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru
Journal of Bionanoscience | Year: 2015

The aim of this article is to investigate the current trends and impact of nanotechnology in induced pluripotent stem cells (iPSCs)-driven tissue engineering and regenerative medicine. The iPSCs are considered as one of the potential cell sources for tissue engineering applications due to their self-renewal and differentiation abilities. However, the key to realize their full potential in tissue engineering requires a deep understanding of the iPSCs biology and their cellular interaction with three-dimensional (3D) scaffolds, which support and regulate the cellular growth and function, in conjunction with signaling molecules. At the cellular and molecular level, nano-scale features play an important role in controlling cell behavior and other physiological functions of iPSCs. Therefore, nanomaterial-based scaffolds have tremendous impact in iPSCs-driven tissue engineering and regenerative medicine. Nanomaterials have been proved to serve as a scaffolding system for tissue engineering, as a carrier system for delivery of cells and genes, and as a marker system for imaging and tracking of iPSCs. In this article, we therefore discuss briefly the impact of nanotechnology on cell behavior and iPSCs-driven tissue engineering and regenerative medicine applications with their recent challenges and advancements.


Rana D.,A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru | Leena M.,Karunya University | Nithyananth M.,Hospital Campus | Pasricha R.,Tata Institute of Fundamental Research | And 3 more authors.
Journal of Nanoscience and Nanotechnology | Year: 2016

Stem cells are considered as an integral part of tissue engineering and regenerative medicine. Cellular functions of stem cells, which are responsible for tissue organization, can be controlled and regulated by providing an appropriate microenvironment, which mimics native stem cell niche. Nanotechnology is a powerful tool for engineering cellular microenvironment in the form of scaffolds. The scaffolds that have nanoscale features, for example, nanofiber, are considered as an effective substratum for tissue regenerative applications because they structurally mimic the native extracellular matrix (ECM). Electrospinning is a technique which produces polymer nanofiber scaffolds with controlled size and orientation of the fibrous structure. These polymer nanofibers can be used to control stem cell fate and function, in particular cell adhesion, proliferation and differentiation, during tissue engineering. In this article, we focus on recent developments and research trends in polymer nanofibrous scaffolds and their impact in controlling and regulating stem cell fate and function. Copyright © 2016 American Scientific Publishers. All rights reserved. Printed in the United States of America.


PubMed | Tohoku University, Dankook University, A Unit of Institute for Stem Cell Biology and Regenerative Medicine Bengaluru, University of Strasbourg and University of South Carolina
Type: | Journal: Acta biomaterialia | Year: 2017

Clinically usable tissue-engineered constructs are currently limited due to their inability of forming microvascular networks necessary for adequate cellular oxygen and nutrient supply upon implantation. The aim of this study is to investigate the conditions necessary for microvascularization in a tissue-engineered construct using vascular endothelial growth factor (VEGF). The construct was made of gelatin methacrylate (GelMA) based cell-laden hydrogel system, which was then covalently linked with VEGF-mimicking peptide (AcQK), using human umbilical vein endothelial cells (HUVECs) as the model cell. The results of the mechanics and gene expression analysis indicated significant changes in mechanical properties and upregulation of vascular-specific genes. The major finding of this study is that the increased expression of vascular-specific genes could be achieved by employing AcQK in the GelMA based hydrogel system, leading to accelerated microvascularization. We conclude that GelMA with covalently-linked angiogenic peptide is a useful tissue engineered construct suitable for microvascularization. STATEMENT OF SIGNIFICANCE: (1) This study reports the conditions necessary for microvascularization in a tissue-engineered construct using vascular endothelial growth factor (VEGF). (2) The construct was made of gelatin methacrylate based cell-laden hydrogel system. (3) There is a significant change observed in mechanical properties and upregulation of vascular-specific genes, in particular CD34, when AcQK is used. (4) The major finding of this study is that the increased expression of vascular-specific genes, i.e., CD34 could be achieved by employing AcQK in the GelMA based hydrogel system, leading to accelerated microvascularization.

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