Harnessing the potential of induced pluripotent stem cells for regenerative medicine

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Recently, research on stem cells has been receiving an increasing amount of attention, both for its advantages and disadvantages. Genetic and epigenetic instabilities among stem cells have been a recurring obstacle to progress in regenerative medicine using stem cells. Various reports have stated that these instabilities can transform stem cells when transferred in vivo and thus have the potential to develop tumors. Previous research has shown that various extrinsic and intrinsic factors can contribute to the stability of stem cells. The extrinsic factors include growth supplements, growth factors, oxygen tension, passage technique, and cryopreservation. Controlling these factors based on previous reports may assist researchers in developing strategies for the production and clinical application of "safe" stem cells. On the other hand, the intrinsic factors can be unpredictable and uncontrollable; therefore, to ensure the successful use of stem cells in regenerative medicine, it is imperative to develop and implement appropriate strategies and technique for culturing stem cells and to confirm the genetic and epigenetic safety of these stem cells before employing them in clinical trials.

Heart disease remains a leading cause of mortality and a major worldwide healthcare burden. Recent advances in stem cell biology have made it feasible to derive large quantities of cardiomyocytes for disease modeling, drug development, and regenerative medicine. The discoveries of reprogramming and transdifferentiation as novel biological processes have significantly contributed to this paradigm. This review surveys the means by which reprogramming and transdifferentiation can be employed to generate induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and induced cardiomyocytes (iCMs). The application of these patient-specific cardiomyocytes for both in vitro disease modeling and in vivo therapies for various cardiovascular diseases will also be discussed. We propose that, with additional refinement, human disease-specific cardiomyocytes will allow us to significantly advance the understanding of cardiovascular disease mechanisms and accelerate the development of novel therapeutic options.

Pluripotent stem cells have gained special attraction because of their almost unlimited proliferation and differentiation capacity in vitro. These properties substantiate the potential of pluripotent stem cells in basic research and regenerative medicine. Here three types of in vitro cultured pluripotent stem cells (embryonic carcinoma, embryonic stem and induced pluripotent stem cells) are compared in their historical context with respect to their different origin and properties. It became evident that tumourigenicity is an inherent property of pluripotent cells based on p53 down-regulation, expression of tumour-related genes and high telomerase activity that allow unlimited proliferation. In addition, culture-adapted genetic and epigenetic changes may induce tumourigenicity of pluripotent cells. The use of stem cells in regenerative medicine, however, requires non-malignant cell types and strategies that circumvent stages of malignancy.Reprogramming strategies of adult somatic cells that avoid the tumourigenic state of pluripotency may offer alternatives for future biomedical application.

Adipose-derived stem cells for regenerative medicine in the field of plastic and reconstructive surgery

From its humble beginnings in bacterial prokaryotic systems and bioprocess engineering, the rapidly expanding field of synthetic biology is now making deep inroads into the field of human clinical therapy. At the same time, the application of stem cells in regenerative medicine has demonstrated much promise in human clinical trials. The convergence of these two disparate disciplines opens up many exciting possibilities, and offers novel solutions to various clinical challenges currently faced in the field of stem cell and regenerative medicine, including: (i) nonspecific pleiotropic effects of growth factors, cytokines, and extracellular matrix molecules on cellular differentiation and lineage fate determination; (ii) the need for intercellular communication and spatiotemporal coordination within 3D tissue-engineered constructs; (iii) safety issues pertaining to genetic modification of human stem cells and the utilization of recombinant DNA and viral vectors; and (iv) limited plasticity and proliferative capacity of adult stem cells and the need for extensive in vitro expansion to attain adequate cell numbers for therapeutic applications. In this review, these challenges are critically examined, together with the relevant safety and ethical issues pertaining to the application of synthetic biology in the field of regenerative medicine.

Non-coding RNAs are promising targets for stem cell-based cancer therapy

HomeCirculationVol. 147, No. 6Stepwise Generation of Human Induced Pluripotent Stem Cell–Derived Cardiac Pericytes to Model Coronary Microvascular Dysfunction No AccessLetterRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessLetterRequest AccessFull TextStepwise Generation of Human Induced Pluripotent Stem Cell–Derived Cardiac Pericytes to Model Coronary Microvascular Dysfunction Mengcheng Shen, PhD, Chun Liu, PhD, Shane Rui Zhao, PhD, Amit Manhas, PhD, Laksshman Sundaram, PhD, Mohamed Ameen, PhD and Joseph C. Wu, MD, PhD Mengcheng ShenMengcheng Shen https://orcid.org/0000-0001-7037-6159 From Stanford Cardiovascular Institute (M.S., C.L., S.R.Z., A.M., M.A., J.C.W.), Stanford University, CA. Institute for Stem Cell Biology and Regenerative Medicine (M.S., C.L., S.R.Z., A.M., J.C.W.), Stanford University, CA. the Departments of Medicine (Division of Cardiology) (M.S., C.L., S.R.Z., A.M., J.C.W.), Stanford University, CA. *M. Shen and C. Liu contributed equally. Search for more papers by this author , Chun LiuChun Liu https://orcid.org/0000-0002-8242-3896 From Stanford Cardiovascular Institute (M.S., C.L., S.R.Z., A.M., M.A., J.C.W.), Stanford University, CA. Institute for Stem Cell Biology and Regenerative Medicine (M.S., C.L., S.R.Z., A.M., J.C.W.), Stanford University, CA. the Departments of Medicine (Division of Cardiology) (M.S., C.L., S.R.Z., A.M., J.C.W.), Stanford University, CA. *M. Shen and C. Liu contributed equally. Search for more papers by this author , Shane Rui ZhaoShane Rui Zhao https://orcid.org/0000-0002-2137-5536 From Stanford Cardiovascular Institute (M.S., C.L., S.R.Z., A.M., M.A., J.C.W.), Stanford University, CA. Institute for Stem Cell Biology and Regenerative Medicine (M.S., C.L., S.R.Z., A.M., J.C.W.), Stanford University, CA. the Departments of Medicine (Division of Cardiology) (M.S., C.L., S.R.Z., A.M., J.C.W.), Stanford University, CA. Search for more papers by this author , Amit ManhasAmit Manhas https://orcid.org/0000-0001-6044-4576 From Stanford Cardiovascular Institute (M.S., C.L., S.R.Z., A.M., M.A., J.C.W.), Stanford University, CA. Institute for Stem Cell Biology and Regenerative Medicine (M.S., C.L., S.R.Z., A.M., J.C.W.), Stanford University, CA. the Departments of Medicine (Division of Cardiology) (M.S., C.L., S.R.Z., A.M., J.C.W.), Stanford University, CA. Illumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA (A.M., L.S.). Search for more papers by this author , Laksshman SundaramLaksshman Sundaram Computer Science (L.S.), Stanford University, CA. Illumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA (A.M., L.S.). Search for more papers by this author , Mohamed AmeenMohamed Ameen From Stanford Cardiovascular Institute (M.S., C.L., S.R.Z., A.M., M.A., J.C.W.), Stanford University, CA. Cancer Biology (M.A.), Stanford University, CA. Search for more papers by this author and Joseph C. WuJoseph C. Wu Correspondence to: Joseph C. Wu, MD, PhD, 265 Campus Drive, Room G1120B, Stanford, CA 94305. Email E-mail Address: [email protected] https://orcid.org/0000-0002-6068-8041 From Stanford Cardiovascular Institute (M.S., C.L., S.R.Z., A.M., M.A., J.C.W.), Stanford University, CA. Institute for Stem Cell Biology and Regenerative Medicine (M.S., C.L., S.R.Z., A.M., J.C.W.), Stanford University, CA. the Departments of Medicine (Division of Cardiology) (M.S., C.L., S.R.Z., A.M., J.C.W.), Stanford University, CA. Search for more papers by this author Originally published6 Feb 2023https://doi.org/10.1161/CIRCULATIONAHA.122.061770Circulation. 2023;147:515–518Footnotes*M. Shen and C. Liu contributed equally.For Sources of Funding and Disclosures, see page 518.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Joseph C. Wu, MD, PhD, 265 Campus Drive, Room G1120B, Stanford, CA 94305. Email [email protected]edu

During the past few decades, there has been enormous progress made in understanding and treating cardiovascular diseases. However, heart failure remains a progressive and debilitating condition with generally poor clinical outcomes and high socio-economic burden. The most common cause of heart failure is caused by loss of functional cardiomyocytes from myocardial infarction and subsequent fibrosis, leading to adverse remodeling, reduced contractile function, and hemodynamic compromise. Given the dire need for better heart failure treatment, investigators have actively explored strategies to improve cardiac function via numerous approaches, including cell transplantation, mechanical device support, or whole organ replacement.1 Although a detailed comparison of the merit of each of these approaches is beyond the scope of this article, one strategy that has captured tremendous interest in recent years is the use of highly potent transcription factors to reprogram cells into an alternative fate. The remarkable finding of Yamanaka and colleagues to revert a fully differentiated cell back to its most primitive state using a combination of transcript factors brought forth widespread optimism that a similar approach can be used successfully to reprogram any somatic cell into a different cell type.2–5 This subsequently led to several follow-on studies to directly reprogram fibroblasts into other cell lineages.6,7 In 2010, one such study by Ieda, Srivastava, and colleagues described the generation of cardiomyocyte-like cells (iCM) by overexpressing Gata4, Mef2c, and Tbx5 (GMT), transcription factors that have been shown to play important roles in cardiac development.8 Although this study reported the generation of 5% to 10% troponin T expressing cells in vitro, 2 follow up studies by Qian et al9 and Song et al10 report the ability of GMT or GMT+Hand1 to reprogram resident cardiac fibroblasts within the failing/fibrotic myocardium into functional …

Liver cell reprogramming

Spermatogonial stem cells are unique cells that line the basal lamina of seminiferous tubules in the testis and have the potential of self-renewal and differentiation. These cells pass on genetic information to the next generation via the process of spermatogenesis and have an important role in the maintenance of male fertility. Recent reports have shown the pluripotency characteristics of spermatogonial stem cells at the cellular and molecular level. These cells can convert into Embryonic stem like cells that exhibit similar phenotype with embryonic stem cells and the capacity to differentiate into all three germ layers: Ectoderm, endoderm and mesoderm. These properties make spermatogonial stem cells an appropriate source for use in regenerative medicine. Spermatogonial stem cells considered as an alternative and novel cell source that limits the technical and ethical problems accompanied with the other pluripotent stem cells. Patient-specific cell lineages without limitations of immunological rejection and specific auto transplantation are the beneficial’s associated with these cell population. Also, cell therapy based on spermatogonial stem cells engraftment, promises for preservation of fertility and induces the reproductive potential in infertile patients. Here, we discuss the applications of spermatogonial stem cells in regenerative medicine with focus on all important aspects, including: cell isolation, propagation, differentiation and especially cell transplantation.

Stem cells in regenerative medicine are advancing rapidly, with significant progress made in recent years. Our bibliometric review is a significant contribution to the field and is essential for advancing research. However, there is a noticeable lack of reviews that focus on stem cells and their clinical applications in regenerative medicine. Our study addressed this gap using advanced tools such as R-Studio and VOSviewer to explore publication volumes, intellectual structures, and emerging trends in the field, ensuring the validity and reliability of our findings. We utilized Scopus and Web of Science to extract 1,274 relevant articles and employed rigorous descriptive analysis, co-occurrence analysis, and text-mining techniques. Our study identified the most influential journals based on productivity and citation volume. These journals are: International Journal of Molecular Sciences, Stem Cell Reviews and Reports, Biomaterials, Stem Cell Research and Therapy, Regenerative Therapy, Stem Cells Translational Medicine, and Cytotherapy. The top-cited articles highlight mRNA, stem cell reprogramming, and innovative therapeutic techniques. Our analysis of the links between stem cells and disease underscores the significant focus on mesenchymal stem cells and pluripotent stem cells, with the most frequently treated conditions being knee osteoarthritis, various types of cancer, and cardiovascular diseases. We also identified emerging areas classified as materials, methods, and technologies such as biopolymers, nanotechnology, deep learning, Kyoto Encyclopedia of Genes and Genomes, three-dimensional printers, and bioprinting. By investigating this focused area, this study provides valuable insights into the current landscape and future directions of stem cell-based regenerative medicine with a clear clinical translation pathway.

Identification and Application of Polymers as Biomaterials for Tissue Engineering and Regenerative Medicine Claire N. Medine, Ferdous Khan, Salvatore Pernagallo, Rong Zhang, Olga Tura, Mark Bradley, and David C. Hay Hydrogel as Stem Cell Niche for In Vivo Applications in Regenerative Medicine Xiaokang Li, Claudia Wittkowske, Rui Yao, and Yanan Du Fabrication and Application of Gradient Hydrogels in Cell and Tissue Engineering Azadeh Seidi, Serge Ostrovidov, and Murugan Ramalingam Smart Biomaterial Scaffold For In Situ Tissue Regeneration Jaehyun Kim, Sunyoung Joo, In Kap Ko, Anthony Atala, James J. Yoo, and Sang Jin Lee Fabrication of 3D Scaffolds and Organ Printing for Tissue Regeneration Ferdous Khan and Sheikh Rafi Ahmad Natural Membranes as Scaffold for Biocompatible Aortic Valve Leaflets: Perspectives from Pericardium? Maria Cristina Vinci, Francesca Prandi, Barbara Micheli, Giulio Tessitore, Anna Guarino, Luca Dainese, Gianluca Polvani, and Maurizio Pesce Spatially Designed Nanofibrous Membranes for Periodontal Tissue Regeneration Marco C. Bottino, Yogesh K. Vohra, and Vinoy Thomas Autoinductive Scaffolds for Osteogenic Differentiation of Mesenchymal Stem Cells Esmaiel Jabbari and Murugan Ramalingam Ophthalmic Applications of Biomaterials in Regenerative Medicine Victoria Kearns, Rosalind Stewart, Sharon Mason, Carl Sheridan, and Rachel Williams Calcium Phosphates as Scaffolds for Mesenchymal Stem Cells Iain R. Gibson Bioactive Glasses as Composite Components: Technological Advantages and Bone Tissue Engineering Applications Elzbieta Pamula, Katarzyna Cholewa-Kowalska, Mariusz Szuta, and Anna M. Osyczka Processing Metallic Biomaterials for a Better Cell Response Ioana Demetrescu, Daniela Ionita, and Cristian Pirvu Osteogenic Adult Stem Cells and Titanium Constructs for Repair and Regeneration Marcus J. Tillotson and Peter M. Brett Stem Cell Response to Biomaterial Topography Luong T.H. Nguyen, Susan Liao, Casey K. Chan, and Seeram Ramakrishna Growth Factors, Stem Cells, Scaffolds and Biomaterials for Tendon Regeneration James Zhenggui Tang, Guo-Qiang Chen, and Nicholas R. Forsyth Biomaterials and Stem Cells for Myocardial Repair Jiashing Yu, Chao-Min Cheng, and Randall J. Lee Perinatal Stem Cells in Regenerative Medicine Bridget M. Deasy, Jordan E. Anderson, Kelley J. Colopietro, and Yong Li Adult Stem Cell Survival Strategies Melanie Rodrigues, Linda G. Griffith, and Alan Wells Immunobiology of Biomaterial/Mesenchymal Stem Cell Interactions Peiman Hematti and Summer Hanson Autologous Mesenchymal Stem Cells for Tissue Engineering in Urology Guihua Liu, Chunhua Deng, and Yuanyuan Zhang Umbilical Cord Matrix Mesenchymal Stem Cells: A Potential Allogenic Cell Source for Tissue Engineering and Regenerative Medicine N.S. Remya and Prabha D. Nair Human Embryonic Stem Cells and Tissue Regeneration Odessa Yabut, Carissa Ritner, and Harold S. Bernstein Clinical Applications of Mesenchymal Stem Cell-Biomaterial Constructs for Tissue Reconstruction Summer Hanson and Peiman Hematti Clinical Aspects of the Use of Stem Cells and Biomaterials for Bone Repair and Regeneration Roger A. Brooks Clinical Translation of Tissue Engineering and Regenerative Medicine Technologies Alejandro Nieponice Index

Advances in stem cell technologies in recent years have generated considerable interest in harnessing the potential of adult and embryonic stem cells in regenerative medicine. Stem cell-based therapies are a particularly attractive option for the treatment of intractable lung diseases for which current therapies are essentially palliative. Proof-of-principle experiments in animal models demonstrate the efficacy of exogenous stem cells in mediating lung repair by attenuating fibrotic responses to injury, but also suggest that their ability to contribute to lung epithelial regeneration and repair is limited. Consequently, attention has turned to endogenous lung stem cells as targets or vehicles for the delivery of lung regenerative therapies. In this article, we discuss the potential and promise of endogenous lung stem cells in regenerative medicine, and the problems and challenges faced by researchers and clinicians in harnessing their potential to repair the lung.