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Role and Application of Stem Cells in Regenerative Medicine 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 55445

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Prof. Dr. Oriana Trubiani

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Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio”, Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
Interests: stem cells; dentistry; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Dr. Guya Marconi

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Department of Innovative Technologies in Clinical Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Interests: regenerative medicine; stem cells; microfluidics; oral stem cells; restorative dentistry; osteoregeneration; biomaterials; epithelial–mesenchymal transition; extracellular vesicles; exosomes; liposomes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue "Role and Application of Stem Cells in Regenerative Medicine" (https://www.mdpi.com/journal/ijms/special_issues/stem_cells_med).

Mesenchymal stem cells (MSCs) are currently being used in preclinical and clinical trials for their aptitude to promote wound healing and tissue regeneration.

In particular, oral-derived mesenchymal stem cells (oral-MSCs) are accessible and can be collected and used in regenerative medicine, avoiding ethical concerns. They can be derived from different oral tissues, such as human exfoliated deciduous teeth (SHED), periodontal ligaments (PDLSCs), dental follicles (as progenitor (P) cells, DFPCs), apical papilla (SCAP), dental pulp (DPSCs), and gingival tissue (GMSCs), and possess multipotential properties and high proliferation and differentiation abilities. Moreover, oral MSCs have paracrine and immunomodulatory capacity, representing an innovative tool for the treatment of various degenerative and traumatic processes, including skeletal and maxilla-facial degeneration, trauma or ischemia injuries, and neurodegenerative as well as immune disorders.

This Special Issue, “Role and Application of Stem Cells in Regenerative Medicine 2.0”, of the International Journal of Molecular Sciences will comprise a selection of research papers and reviews contributing to the evaluation of the aptitude of oral-MSCs in particular and their secretome for tissue regeneration, as a starting point for the fabrication of 3D-living constructs for future clinical applications.

Moreover, in vitro and in vivo studies on the molecular mechanisms involved in tissue regeneration are of interest, since they will provide a possibly important contribution to the development of stem cell-based regeneration strategies and to the identification of key biological regulation processes that remain uncovered.

Prof. Dr. Oriana Trubiani
Dr. Guya Diletta Marconi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Mesenchymal stem cells
Tissue regeneration
Regenerative medicine
Immunomodulatory process

Related Special Issues

Role and Application of Stem Cells in Regenerative Medicine in International Journal of Molecular Sciences (32 articles)
Role and Application of Stem Cells in Regenerative Medicine 3.0 in International Journal of Molecular Sciences (6 articles)

Published Papers (12 papers)

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Editorial

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9 pages, 831 KiB

Open AccessEditorial

Stem Cells Secretome from Oral Tissue Could Represent a Promising Therapeutic Approach in COVID-19-Disease?

by Francesca Diomede, Guya D. Marconi, Luigia Fonticoli, Jacopo Pizzicannella and Oriana Trubiani

Int. J. Mol. Sci. 2020, 21(18), 6833; https://doi.org/10.3390/ijms21186833 - 17 Sep 2020

Cited by 3 | Viewed by 2323

Abstract

At present, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has quickly become a health emergency because no specifics vaccines or drugs, at this moment, are available. Recent studies have shown that the transplantation of mesenchymal stem cells (MSCs) into Coronavirus Disease 2019 (COVID-19) patients could represent a promising strategy for the development of new therapeutic methods. We speculate and suggest that the secretome of human Oral Tissue Stem Cells (hOTSCs), for their immunomodulatory and anti-inflammatory specific properties, could exert beneficial effects on the COVID-19 patients through an innovative aerosolisation technique. This non-invasive technique can offer multiple advantages in prophylaxis, as well as the prevention and treatment of severe epidemic respiratory syndrome with minimum risk and optimal therapeutic effects. This has the potential to create a novel pathway towards immunomodulatory therapy for the treatment of COVID-19 positive patients. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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Research

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27 pages, 4560 KiB

Open AccessArticle

Umbilical Cord-Derived Mesenchymal Stem Cells Are Able to Use bFGF Treatment and Represent a Superb Tool for Immunosuppressive Clinical Applications

by Lenka Tesarova, Klara Jaresova, Pavel Simara and Irena Koutna

Int. J. Mol. Sci. 2020, 21(15), 5366; https://doi.org/10.3390/ijms21155366 - 28 Jul 2020

Cited by 17 | Viewed by 4731

Abstract

Mesenchymal stem cells (MSCs) have become a promising tool in cellular therapy for restoring immune system haemostasis; however, the success of clinical trials has been impaired by the lack of standardized manufacturing processes. This study aims to determine the suitability of source tissues and culture media for the production of MSC-based advanced therapy medicinal products (ATMPs) and to define parameters to extend the set of release criteria. MSCs were isolated from umbilical cord (UC), bone marrow and lipoaspirate and expanded in three different culture media. MSC phenotype, proliferation capacity and immunosuppressive parameters were evaluated in normal MSCs compared to primed MSCs treated with cytokines mimicking an inflammatory environment. Compared to bone marrow and lipoaspirate, UC-derived MSCs (UC-MSCs) showed the highest proliferative capacity, which was further enhanced by media supplemented with bFGF, while the cells maintained their immunosuppressive characteristics. Moreover, UC-MSCs expanded in the bFGF-enriched medium were the least sensitive to undesirable priming-induced changes in the MSC phenotype. Surface markers and secreted factors were identified to reflect the cell response to inflammatory priming and to be variable among MSCs from different source tissues. This study demonstrates that UC is a favorable cell source for manufacturing MSC-based ATMPs for immunosuppressive applications. UC-MSCs are able to use the bFGF-enriched medium for higher cell yields without the impairment of immunosuppressive parameters and undesirable phenotype changes after inflammatory preconditioning of MSCs before transplantation. Additionally, immunosuppressive parameters were identified to help finding predictors of clinically efficient MSCs in the following clinical trials. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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21 pages, 2769 KiB

Open AccessArticle

Stem Cell Conditioned Medium Treatment for Canine Spinal Cord Injury: Pilot Feasibility Study

by Zuzana Vikartovska, Maria Kuricova, Jana Farbakova, Tomas Liptak, Dagmar Mudronova, Filip Humenik, Aladar Madari, Marcela Maloveska, Eva Sykova and Dasa Cizkova

Int. J. Mol. Sci. 2020, 21(14), 5129; https://doi.org/10.3390/ijms21145129 - 20 Jul 2020

Cited by 16 | Viewed by 4060

Abstract

Spinal cord injury (SCI) involves nerve damage and often leads to motor, sensory and autonomic dysfunctions. In the present study, we have designed a clinical protocol to assess the feasibility of systemic delivery of allogenic canine bone marrow tissue-derived mesenchymal stem cell conditioned medium (BMMSC CM) to dogs with SCI. Four client-owned dogs with chronic SCI lasting more than six months underwent neurological and clinical evaluation, MRI imaging and blood tests before being enrolled in this study. All dogs received four intravenous infusions with canine allogenic BMMSC CM within one month. Between the infusions the dogs received comprehensive physiotherapy, which continued for three additional months. No adverse effects or complications were observed during the one, three and six months follow-up periods. Neither blood chemistry panel nor hematology profile showed any significant changes. All dogs were clinically improved as assessed using Olby locomotor scales after one, three and six months of BMMSC CM treatment. Furthermore, goniometric measurements revealed partial improvement in the range of joint motion. Bladder function improved in two disabled dogs. We conclude that multiple delivery of allogenic cell-derived conditioned medium to dogs with chronic SCI is feasible, and it might be clinically beneficial in combination with physiotherapy. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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23 pages, 5068 KiB

Open AccessArticle

Self-Organized Liver Microtissue on a Bio-Functional Surface: The Role of Human Adipose-Derived Stromal Cells in Hepatic Function

by Seokheon Hong, Seung Ja Oh, Dongho Choi, Yongsung Hwang and Sang-Heon Kim

Int. J. Mol. Sci. 2020, 21(13), 4605; https://doi.org/10.3390/ijms21134605 - 29 Jun 2020

Cited by 4 | Viewed by 2662

Abstract

The maintenance of hepatocyte function is a critical research topic in liver tissue engineering. Although an increasing number of strategies have been developed, liver tissue engineering using hepatocytes as a therapeutic alternative remains challenging owing to its poor efficacy. In this study, we developed a multicellular hepatic microtissue to enhance the function of induced hepatic precursor cells. Mouse induced hepatic precursor cells (miHeps) were self-organized in 3D with human adipose-derived stem cells (hASCs) on a bio-functional matrix. We found that hepatic phenotypes, such as levels of albumin, asialoglycoprotein receptor-1, and cytochrome P450, were enhanced in miHeps-hASC microtissue comprising miHeps and hASCs relative to two-dimensional-cultured miHeps-hASCs. Additionally, the secretome of 3D-cultured hASCs increased the hepatic function of mature miHeps. Furthermore, hepatic gene expression was reduced in mature miHeps treated with conditioned media of hypoxia-inducible factor 1α (HIF1α)-depleted hASCs relative to that with conditioned media of control hASCs. Our results suggested that the hepatic function of 3D-co-cultured miHeps could be enhanced by HIF1α-dependent factors secreted from stromal cells. This study provides an insight into the factors regulating hepatic function and shows that self-organized hepatic microtissue could act as liver spheroids for liver regenerative medicine and liver toxicity tests. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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21 pages, 4140 KiB

Open AccessArticle

Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance

by Chieh Yu, Ian W. Peall, Son H. Pham, Rachel K. Okolicsanyi, Lyn R. Griffiths and Larisa M. Haupt

Int. J. Mol. Sci. 2020, 21(11), 3884; https://doi.org/10.3390/ijms21113884 - 29 May 2020

Cited by 13 | Viewed by 3821

Abstract

Bone marrow-derived human mesenchymal stems cells (hMSCs) are precursors to adipocyte and osteoblast lineage cells. Dysregulation of the osteo-adipogenic balance has been implicated in pathological conditions involving bone loss. Heparan sulfate proteoglycans (HSPGs) such as cell membrane-bound syndecans (SDCs) and glypicans (GPCs) mediate hMSC lineage differentiation and with syndecan-1 (SDC-1) reported in both adipogenesis and osteogenesis, these macromolecules are potential regulators of the osteo-adipogenic balance. Here, we disrupted the HSPG profile in primary hMSC cultures via temporal knockdown (KD) of SDC-1 using RNA interference (RNAi) in undifferentiated, osteogenic and adipogenic differentiated hMSCs. SDC-1 KD cultures were examined for osteogenic and adipogenic lineage markers along with changes in HSPG profile and common signalling pathways implicated in hMSC lineage fate. Undifferentiated hMSC SDC-1 KD cultures exhibited a pro-adipogenic phenotype with subsequent osteogenic differentiation demonstrating enhanced maturation of osteoblasts. In cultures where SDC-1 KD was performed following initiation of differentiation, increased adipogenic gene and protein marker expression along with increased Oil Red O staining identified enhanced adipogenesis, with impaired osteogenesis also observed in these cultures. These findings implicate SDC-1 as a facilitator of the hMSC osteo-adipogenic balance during early induction of lineage differentiation. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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14 pages, 3063 KiB

Open AccessArticle

Recovery of Tendon Characteristics by Inhibition of Aberrant Differentiation of Tendon-Derived Stem Cells from Degenerative Tendinopathy

by Sun Jeong Kim, Hae Won Oh, Jong Wook Chang and Sang Jun Kim

Int. J. Mol. Sci. 2020, 21(8), 2687; https://doi.org/10.3390/ijms21082687 - 13 Apr 2020

Cited by 5 | Viewed by 2235

Abstract

The inhibition of the aberrant differentiation of tendon-derived stem cells (TDSCs) is a major target for the regeneration of damaged tendon tissues, as tendinopathy can be caused by the aberrant differentiation of TDSCs. We investigated whether the possible aberrant differentiation of TDSCs can be prevented by using adequate inhibitors. TDSCs extracted from chemically induced tendinopathy and injury-with-overuse tendinopathy models were cultured with 18α-glycyrrhetinic acid (AGA) and T0070907 to block osteogenic differentiation and adipogenic differentiation, respectively. The optimal dose of AGA decreased the osteogenic-specific marker Runx2 (Runt-related transcription factor 2), and T0070907 blocked the adipogenic-specific marker peroxisome proliferator-activated receptor gamma (PPARγ) in mRNA levels. We also found that AGA induced tenogenic differentiation in mRNA levels. However, T0070907 did not affect the tenogenic differentiation and regenerative capacity of TDSCs. We expect that optimal doses of AGA and T0070907 can prevent tendinopathy by inhibiting osteogenic and adipogenic differentiation, respectively. In addition, AGA and T0070907 may play important roles in the treatment of tendinopathy. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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24 pages, 2677 KiB

Open AccessArticle

MicroRNA-29a Exhibited Pro-Angiogenic and Anti-Fibrotic Features to Intensify Human Umbilical Cord Mesenchymal Stem Cells—Renovated Perfusion Recovery and Preventing against Fibrosis from Skeletal Muscle Ischemic Injury

by Wen-Hong Su, Ching-Jen Wang, Yi-Yung Hung, Chun-Wun Lu, Chia-Yu Ou, Shun-Hung Tseng, Ching-Chin Tsai, Yun-Ting Kao and Pei-Chin Chuang

Int. J. Mol. Sci. 2019, 20(23), 5859; https://doi.org/10.3390/ijms20235859 - 22 Nov 2019

Cited by 5 | Viewed by 3085

Abstract

This study was conducted to elucidate whether microRNA-29a (miR-29a) and/or together with transplantation of mesenchymal stem cells isolated from umbilical cord Wharton’s jelly (uMSCs) could aid in skeletal muscle healing and putative molecular mechanisms. We established a skeletal muscle ischemic injury model by injection of a myotoxin bupivacaine (BPVC) into gastrocnemius muscle of C57BL/6 mice. Throughout the angiogenic and fibrotic phases of muscle healing, miR-29a was considerably downregulated in BPVC-injured gastrocnemius muscle. Overexpressed miR-29a efficaciously promoted human umbilical vein endothelial cells proliferation and capillary-like tube formation in vitro, crucial steps for neoangiogenesis, whereas knockdown of miR-29a notably suppressed those endothelial functions. Remarkably, overexpressed miR-29a profitably elicited limbic flow perfusion and estimated by Laser Dopple. MicroRNA-29a motivated perfusion recovery through abolishing the tissue inhibitor of metalloproteinase (TIMP)-2, led great numbers of pro-angiogenic matrix metalloproteinases (MMPs) to be liberated from bondage of TIMP, thus reinforced vascular development. Furthermore, engrafted uMSCs also illustrated comparable effect to restore the flow perfusion and augmented vascular endothelial growth factors-A, -B, and -C expression. Notably, the combination of miR29a and the uMSCs treatments revealed the utmost renovation of limbic flow perfusion. Amplified miR-29a also adequately diminished the collagen deposition and suppressed broad-wide miR-29a targeted extracellular matrix components expression. Consistently, miR-29a administration intensified the relevance of uMSCs to abridge BPVC-aggravated fibrosis. Our data support that miR-29a is a promising pro-angiogenic and anti-fibrotic microRNA which delivers numerous advantages to endorse angiogenesis, perfusion recovery, and protect against fibrosis post injury. Amalgamation of nucleic acid-based strategy (miR-29a) together with the stem cell-based strategy (uMSCs) may be an innovative and eminent strategy to accelerate the healing process post skeletal muscle injury. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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Review

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13 pages, 1221 KiB

Open AccessReview

The Use of Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells in Articular Cartilage Regeneration: A Review

by Parviz Vahedi, Rana Moghaddamshahabi, Thomas J. Webster, Ayse Ceren Calikoglu Koyuncu, Elham Ahmadian, Wasim S. Khan, Ali Jimale Mohamed and Aziz Eftekhari

Int. J. Mol. Sci. 2021, 22(17), 9215; https://doi.org/10.3390/ijms22179215 - 26 Aug 2021

Cited by 56 | Viewed by 4189

Abstract

Cartilage is frequently damaged with a limited capacity for repair. Current treatment strategies are insufficient as they form fibrocartilage as opposed to hyaline cartilage, and do not prevent the progression of degenerative changes. There is increasing interest in the use of autologous mesenchymal stem cells (MSC) for tissue regeneration. MSCs that are used to treat articular cartilage defects must not only present a robust cartilaginous production capacity, but they also must not cause morbidity at the harvest site. In addition, they should be easy to isolate from the tissue and expand in culture without terminal differentiation. The source of MSCs is one of the most important factors that may affect treatment. The infrapatellar fat pad (IPFP) acts as an important reservoir for MSC and is located in the anterior compartment of the knee joint in the extra-synovial area. The IPFP is a rich source of MSCs, and in this review, we discuss studies that demonstrate that these cells have shown many advantages over other tissues in terms of ease of isolation, expansion, and chondrogenic differentiation. Future studies in articular cartilage repair strategies and suitable extraction as well as cell culture methods will extend the therapeutical application of IPFP-derived MSCs into additional orthopedic fields, such as osteoarthritis. This review provides the latest research concerning the use of IPFP-derived MSCs in the treatment of articular cartilage damage, providing critical information for the field to grow. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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18 pages, 983 KiB

Open AccessReview

Signaling Molecules Regulating Pancreatic Endocrine Development from Pluripotent Stem Cell Differentiation

by Hui Huang, Taylor N. Bader and Sha Jin

Int. J. Mol. Sci. 2020, 21(16), 5867; https://doi.org/10.3390/ijms21165867 - 15 Aug 2020

Cited by 9 | Viewed by 4586

Abstract

Diabetes is one of the leading causes of death globally. Currently, the donor pancreas is the only source of human islets, placing extreme constraints on supply. Hence, it is imperative to develop renewable islets for diabetes research and treatment. To date, extensive efforts have been made to derive insulin-secreting cells from human pluripotent stem cells with substantial success. However, the in vitro generation of functional islet organoids remains a challenge due in part to our poor understanding of the signaling molecules indispensable for controlling differentiation pathways towards the self-assembly of functional islets from stem cells. Since this process relies on a variety of signaling molecules to guide the differentiation pathways, as well as the culture microenvironments that mimic in vivo physiological conditions, this review highlights extracellular matrix proteins, growth factors, signaling molecules, and microenvironments facilitating the generation of biologically functional pancreatic endocrine cells from human pluripotent stem cells. Signaling pathways involved in stepwise differentiation that guide the progression of stem cells into the endocrine lineage are also discussed. The development of protocols enabling the generation of islet organoids with hormone release capacities equivalent to native adult islets for clinical applications, disease modeling, and diabetes research are anticipated. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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17 pages, 1512 KiB

Open AccessReview

Genetically Modified Mesenchymal Stem Cells: The Next Generation of Stem Cell-Based Therapy for TBI

by Rami Ahmad Shahror, Chung-Che Wu, Yung-Hsiao Chiang and Kai-Yun Chen

Int. J. Mol. Sci. 2020, 21(11), 4051; https://doi.org/10.3390/ijms21114051 - 05 Jun 2020

Cited by 21 | Viewed by 5150

Abstract

Mesenchymal stem cells (MSCs) are emerging as an attractive approach for restorative medicine in central nervous system (CNS) diseases and injuries, such as traumatic brain injury (TBI), due to their relatively easy derivation and therapeutic effect following transplantation. However, the long-term survival of the grafted cells and therapeutic efficacy need improvement. Here, we review the recent application of MSCs in TBI treatment in preclinical models. We discuss the genetic modification approaches designed to enhance the therapeutic potency of MSCs for TBI treatment by improving their survival after transplantation, enhancing their homing abilities and overexpressing neuroprotective and neuroregenerative factors. We highlight the latest preclinical studies that have used genetically modified MSCs for TBI treatment. The recent developments in MSCs’ biology and potential TBI therapeutic targets may sufficiently improve the genetic modification strategies for MSCs, potentially bringing effective MSC-based therapies for TBI treatment in humans. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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26 pages, 632 KiB

Open AccessReview

Stem Cells Therapy for Spinal Cord Injury: An Overview of Clinical Trials

by Serena Silvestro, Placido Bramanti, Oriana Trubiani and Emanuela Mazzon

Int. J. Mol. Sci. 2020, 21(2), 659; https://doi.org/10.3390/ijms21020659 - 19 Jan 2020

Cited by 58 | Viewed by 11656

Abstract

Spinal cord injury (SCI) is a traumatic lesion that causes disability with temporary or permanent sensory and/or motor deficits. The pharmacological approach still in use for the treatment of SCI involves the employment of corticosteroid drugs. However, SCI remains a very complex disorder that needs future studies to find effective pharmacological treatments. SCI actives a strong inflammatory response that induces a loss of neurons followed by a cascade of events that lead to further spinal cord damage. Many experimental studies demonstrate the therapeutic effect of stem cells in SCI due to their capacity to differentiate into neuronal cells and by releasing neurotrophic factors. Therefore, they appear to be a valid strategy to use in the field of regenerative medicine. The purpose of this paper is to provide an overview of clinical trials, recorded in clinical trial.gov during 2005–2019, aimed to evaluate the use of stem cell-based therapy in SCI. The results available thus far show the safety and efficacy of stem cell therapy in patients with SCI. However, future trials are needed to investigate the safety and efficacy of stem cell transplantation. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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16 pages, 2307 KiB

Open AccessReview

Stem Cells: The Game Changers of Human Cardiac Disease Modelling and Regenerative Medicine

by Elvira Immacolata Parrotta, Stefania Scalise, Luana Scaramuzzino and Giovanni Cuda

Int. J. Mol. Sci. 2019, 20(22), 5760; https://doi.org/10.3390/ijms20225760 - 16 Nov 2019

Cited by 19 | Viewed by 5911

Abstract

A comprehensive understanding of the molecular basis and mechanisms underlying cardiac diseases is mandatory for the development of new and effective therapeutic strategies. The lack of appropriate in vitro cell models that faithfully mirror the human disease phenotypes has hampered the understanding of molecular insights responsible of heart injury and disease development. Over the past decade, important scientific advances have revolutionized the field of stem cell biology through the remarkable discovery of reprogramming somatic cells into induced pluripotent stem cells (iPSCs). These advances allowed to achieve the long-standing ambition of modelling human disease in a dish and, more interestingly, paved the way for unprecedented opportunities to translate bench discoveries into new therapies and to come closer to a real and effective stem cell-based medicine. The possibility to generate patient-specific iPSCs, together with the new advances in stem cell differentiation procedures and the availability of novel gene editing approaches and tissue engineering, has proven to be a powerful combination for the generation of phenotypically complex, pluripotent stem cell-based cellular disease models with potential use for early diagnosis, drug screening, and personalized therapy. This review will focus on recent progress and future outcome of iPSCs technology toward a customized medicine and new therapeutic options. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 2.0)

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