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Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges

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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 (19 March 2021) | Viewed by 47479

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Dr. Tullia Maraldi

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Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Interests: stem cells and age-related disorders
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Valentina Russo

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Faculty of Bioscience and Agro-Food and Environmental Technology, Agriculture and Environment, University of Teramo, Via Renato Balzarini 1, 64100 Teramo, Italy
Interests: regenerative medicine; tissue engineering; amniotic-derived stem cells
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

Significant recent advances in the regenerative therapy have intensified the research on different sources of stem cells.

Although embryonic and adult tissues can be used for the isolation of pluripotent stem cells, significant limitations, including ethical concerns, complexity of isolation/culture and tumorigenicity, have hindered translation of laboratory findings into clinical practice.

Stem cell research drew the attention toward amniotic membrane and amniotic fluid stem cells, since these sources possess many advantages: first of all cells can be extracted from discarded fetal material, secondly abundant stem cells can be obtained and finally, these stem cell sources are free from ethical considerations and tumorigenicity. Stem cells derived from amniotic fluid and membranes possess embryonic stem cell-like differentiation capability and, similar to mesenchymal stem cells, are also able to modulate the local immune response. Their reduced immunogenicity and immunomodulatory properties allow their use in allo and xeno-transplantation settings. These, and other properties, make these cells attractive for cellular therapy.

This Special Issue on “Amniotic fluid and placental membranes as sources of stem cells: progress and challenges” welcomes original research articles that illustrate and stimulate the growing efforts to understand the implication of stem cells in pathological conditions such as cardiovascular and metabolic diseases, inflammatory, autoimmune, skeletal and degenerative diseases.

Dr. Tullia Maraldi
Prof. Valentina Russo
Guest Editors

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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.

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Keywords

Amniotic fluid stem cells
Amniotic epithelial stem cells
Placental stem cells
Regenerative therapy
Immunomodulation
Secretome
Exosomes
Degenerative diseases
Inflammatory diseases

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Amniotic Fluid and Placental Membranes as Sources of Stem Cells 2.0 in International Journal of Molecular Sciences (19 articles)

Published Papers (12 papers)

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Editorial

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6 pages, 184 KiB

Open AccessEditorial

Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges

by Tullia Maraldi and Valentina Russo

Int. J. Mol. Sci. 2022, 23(10), 5362; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105362 - 11 May 2022

Cited by 5 | Viewed by 1445

Abstract

The intention of this special edition is to collect review and original research articles that illustrate and stimulate growing efforts to understand the implication of perinatal stem cells in pathological conditions such as cardiovascular and metabolic diseases and inflammatory, autoimmune, musculoskeletal, and degenerative [...] Read more.

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

Research

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32 pages, 6655 KiB

Open AccessArticle

Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells

by Ambra Costa, Davide Ceresa, Antonella De Palma, Rossana Rossi, Sara Turturo, Sara Santamaria, Carolina Balbi, Federico Villa, Daniele Reverberi, Katia Cortese, Pierangela De Biasio, Dario Paladini, Domenico Coviello, Silvia Ravera, Paolo Malatesta, Pierluigi Mauri, Rodolfo Quarto and Sveva Bollini

Int. J. Mol. Sci. 2021, 22(7), 3713; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073713 - 02 Apr 2021

Cited by 14 | Viewed by 3901

Abstract

We previously reported that c-KIT+ human amniotic-fluid derived stem cells obtained from leftover samples of routine II trimester prenatal diagnosis (fetal hAFS) are endowed with regenerative paracrine potential driving pro-survival, anti-fibrotic and proliferative effects. hAFS may also be isolated from III trimester clinical waste samples during scheduled C-sections (perinatal hAFS), thus offering a more easily accessible alternative when compared to fetal hAFS. Nonetheless, little is known about the paracrine profile of perinatal hAFS. Here we provide a detailed characterization of the hAFS total secretome (i.e., the entirety of soluble paracrine factors released by cells in the conditioned medium, hAFS-CM) and the extracellular vesicles (hAFS-EVs) within it, from II trimester fetal- versus III trimester perinatal cells. Fetal- and perinatal hAFS were characterized and subject to hypoxic preconditioning to enhance their paracrine potential. hAFS-CM and hAFS-EV formulations were analyzed for protein and chemokine/cytokine content, and the EV cargo was further investigated by RNA sequencing. The phenotype of fetal- and perinatal hAFS, along with their corresponding secretome formulations, overlapped; yet, fetal hAFS showed immature oxidative phosphorylation activity when compared to perinatal ones. The profiling of their paracrine cargo revealed some differences according to gestational stage and hypoxic preconditioning. Both cell sources provided formulations enriched with neurotrophic, immunomodulatory, anti-fibrotic and endothelial stimulating factors, and the immature fetal hAFS secretome was defined by a more pronounced pro-vasculogenic, regenerative, pro-resolving and anti-aging profile. Small RNA profiling showed microRNA enrichment in both fetal- and perinatal hAFS-EV cargo, with a stably- expressed pro-resolving core as a reference molecular signature. Here we confirm that hAFS represents an appealing source of regenerative paracrine factors; the selection of either fetal or perinatal hAFS secretome formulations for future paracrine therapy should be evaluated considering the specific clinical scenario. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

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19 pages, 6052 KiB

Open AccessArticle

Conditioned Medium from Human Amnion-Derived Mesenchymal Stromal/Stem Cells Attenuating the Effects of Cold Ischemia-Reperfusion Injury in an In Vitro Model Using Human Alveolar Epithelial Cells

by Vitale Miceli, Alessandro Bertani, Cinzia Maria Chinnici, Matteo Bulati, Mariangela Pampalone, Giandomenico Amico, Claudia Carcione, Eva Schmelzer, Jörg C. Gerlach and Pier Giulio Conaldi

Int. J. Mol. Sci. 2021, 22(2), 510; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020510 - 06 Jan 2021

Cited by 20 | Viewed by 2485

Abstract

The clinical results of lung transplantation (LTx) are still less favorable than other solid organ transplants in both the early and long term. The fragility of the lungs limits the procurement rate and can favor the occurrence of ischemia-reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) with Steen Solution^TM (SS) aims to address problems, and the implementation of EVLP to alleviate the activation of IRI-mediated processes has been achieved using mesenchymal stromal/stem cell (MSC)-based treatments. In this study, we investigated the paracrine effects of human amnion-derived MSCs (hAMSCs) in an in vitro model of lung IRI that includes cold ischemia and normothermic EVLP. We found that SS enriched by a hAMSC-conditioned medium (hAMSC-CM) preserved the viability and delayed the apoptosis of alveolar epithelial cells (A549) through the downregulation of inflammatory factors and the upregulation of antiapoptotic factors. These effects were more evident using the CM of 3D hAMSC cultures, which contained an increased amount of immunosuppressive and growth factors compared to both 2D cultures and encapsulated-hAMSCs. To conclude, we demonstrated an in vitro model of lung IRI and provided evidence that a hAMSC-CM attenuated IRI effects by improving the efficacy of EVLP, leading to strategies for a potential implementation of this technique. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

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17 pages, 2479 KiB

Open AccessArticle

Amniotic Fluid Stem Cell-Derived Extracellular Vesicles Counteract Steroid-Induced Osteoporosis In Vitro

by Martina Gatti, Francesca Beretti, Manuela Zavatti, Emma Bertucci, Soraia Ribeiro Luz, Carla Palumbo and Tullia Maraldi

Int. J. Mol. Sci. 2021, 22(1), 38; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010038 - 22 Dec 2020

Cited by 21 | Viewed by 2455

Abstract

Background—Osteoporosis is characterized by defects in both quality and quantity of bone tissue, which imply high susceptibility to fractures with limitations of autonomy. Current therapies for osteoporosis are mostly concentrated on how to inhibit bone resorption but give serious adverse effects. Therefore, more effective and safer therapies are needed that even encourage bone formation. Here we examined the effect of extracellular vesicles secreted by human amniotic fluid stem cells (AFSC) (AFSC-EV) on a model of osteoporosis in vitro. Methods—human AFSC-EV were added to the culture medium of a human pre-osteoblast cell line (HOB) induced to differentiate, and then treated with dexamethasone as osteoporosis inducer. Aspects of differentiation and viability were assessed by immunofluorescence, Western blot, mass spectrometry, and histological assays. Since steroids induce oxidative stress, the levels of reactive oxygen species and of redox related proteins were evaluated. Results—AFSC-EV were able to ameliorate the differentiation ability of HOB both in the case of pre-osteoblasts and when the differentiation process was affected by dexamethasone. Moreover, the viability was increased and parallelly apoptotic markers were reduced. The presence of EV positively modulated the redox unbalance due to dexamethasone. Conclusion—these findings demonstrated that EV from hAFSC have the ability to recover precursor cell potential and delay local bone loss in steroid-related osteoporosis. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

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12 pages, 2160 KiB

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Prophylactic Therapy with Human Amniotic Fluid Stem Cells Improves Long-Term Cognitive Impairment in Rat Neonatal Sepsis Survivors

by Yushi Abe, Daigo Ochiai, Yu Sato, Seiji Kanzaki, Satoru Ikenoue, Yoshifumi Kasuga and Mamoru Tanaka

Int. J. Mol. Sci. 2020, 21(24), 9590; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249590 - 16 Dec 2020

Cited by 8 | Viewed by 2009

Abstract

A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

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20 pages, 6674 KiB

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The Effect of Angiotensin II, Retinoic Acid, EGCG, and Vitamin C on the Cardiomyogenic Differentiation Induction of Human Amniotic Fluid-Derived Mesenchymal Stem Cells

by Monika Gasiūnienė, Elvina Valatkaitė, Aistė Navakauskaitė and Rūta Navakauskienė

Int. J. Mol. Sci. 2020, 21(22), 8752; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228752 - 19 Nov 2020

Cited by 5 | Viewed by 2123

Abstract

Human amniotic fluid-derived mesenchymal stem cells (AF-MSCs) may be potentially applied in cell therapy or regenerative medicine as a new alternative source of stem cells. They could be particularly valuable in restoring cardiac tissue after myocardial infarction or other cardiovascular diseases. We investigated the potential of biologically active compounds, namely, angiotensin II, retinoic acid (RA), epigallocatechin-3-gallate (EGCG), vitamin C alone, and the combinations of RA, EGCG, and vitamin C with angiotensin II to induce cardiomyogenic differentiation of AF-MSCs. We observed that the upregulated expression of cardiac gene markers (NKX2-5, MYH6, TNNT2, and DES) and cardiac ion channel genes (sodium, calcium, the potassium) as well as the increased levels of Connexin 43 and Nkx2.5 proteins. Extracellular flux analysis, applied for the first time on AF-MSCs induced with biologically active compounds, revealed the switch in AF-MSCs energetic phenotype and enhanced utilization of oxidative phosphorylation for energy production. Moreover, we demonstrated changes in epigenetic marks associated with transcriptionally active (H3K4me3, H3K9ac, and H4hyperAc) or repressed (H3K27me3) chromatin. All in all, we demonstrated that explored biomolecules were able to induce alterations in AF-MSCs at the phenotypic, genetic, protein, metabolic, and epigenetic levels, leading to the formation of cardiomyocyte progenitors that may become functional heart cells in vitro or in vivo. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

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16 pages, 4473 KiB

Open AccessArticle

Human Mesenchymal Stromal Cells Unveil an Unexpected Differentiation Potential toward the Dopaminergic Neuronal Lineage

by Giulia Gaggi, Andrea Di Credico, Pascal Izzicupo, Francesco Alviano, Michele Di Mauro, Angela Di Baldassarre and Barbara Ghinassi

Int. J. Mol. Sci. 2020, 21(18), 6589; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186589 - 09 Sep 2020

Cited by 12 | Viewed by 2824

Abstract

Degeneration of dopaminergic neurons represents the cause of many neurodegenerative diseases, with increasing incidence worldwide. The replacement of dead cells with new healthy ones may represent an appealing therapeutic approach to these pathologies, but currently, only pluripotent stem cells can generate dopaminergic neurons with high efficiency. However, with the use of these cells arises safety and/or ethical issues. Human mesenchymal stromal cells (hFM-MSCs) are perinatal stem cells that can be easily isolated from the amniochorionic membrane after delivery. Generally considered multipotent, their real differentiative potential is not completely elucidated. The aim of this study was to analyze their stemness characteristics and to evaluate whether they may overcome their mesenchymal fate, generating dopaminergic neurons. We demonstrated that hFM-MSCs expressed embryonal genes OCT4, NANOG, SOX2, KLF4, OVOL1, and ESG1, suggesting they have some features of pluripotency. Moreover, hFM-MSCs that underwent a dopaminergic differentiation protocol gradually increased the transcription of dopaminergic markers LMX1b, NURR1, PITX3, and DAT. We finally obtained a homogeneous population of cells resembling the morphology of primary midbrain dopaminergic neurons that expressed the functional dopaminergic markers TH, DAT, and Nurr1. In conclusion, our results suggested that hFM-MSCs retain the expression of pluripotency genes and are able to differentiate not only into mesodermal cells, but also into neuroectodermal dopaminergic neuron-like cells. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

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19 pages, 7048 KiB

Open AccessArticle

Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells

by Maria Camilla Ciardulli, Luigi Marino, Erwin Pavel Lamparelli, Maurizio Guida, Nicholas Robert Forsyth, Carmine Selleri, Giovanna Della Porta and Nicola Maffulli

Int. J. Mol. Sci. 2020, 21(16), 5905; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21165905 - 17 Aug 2020

Cited by 21 | Viewed by 3823

Abstract

Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to human Growth Differentiation Factor 5 (hGDF-5) we supplemented each at doses of 1, 10, and 100 ng/mL of hGDF-5 and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated the expression of collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis-A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed up-regulation of SCX-A (1.7-fold) at Day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX-A (3.8-fold) and TNC (2.3-fold) after three days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular-shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this, we explored the expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines up-regulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold), but a greater up-regulation of IL-10 (2.5-fold). Type 1 collagen and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification with a length/width ratio increase, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue-engineering protocols. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

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Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells

by Quan-Wen Liu, Qi-Ming Huang, Han-You Wu, Guo-Si-Lang Zuo, Hao-Cheng Gu, Ke-Yu Deng and Hong-Bo Xin

Int. J. Mol. Sci. 2021, 22(2), 970; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020970 - 19 Jan 2021

Cited by 57 | Viewed by 8709

Abstract

Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells (ASCs) are able to repair/replace damaged or degenerative tissues and improve functional recovery in experimental model and clinical trials. However, there are still many limitations and unresolved problems regarding stem cell therapy in terms of ethical barriers, immune rejection, tumorigenicity, and cell sources. By reviewing recent literatures and our related works, human amnion-derived stem cells (hADSCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) have shown considerable advantages over other stem cells. In this review, we first described the biological characteristics and advantages of hADSCs, especially for their high pluripotency and immunomodulatory effects. Then, we summarized the therapeutic applications and recent progresses of hADSCs in treating various diseases for preclinical research and clinical trials. In addition, the possible mechanisms and the challenges of hADSCs applications have been also discussed. Finally, we highlighted the properties of hADSCs as a promising source of stem cells for cell therapy and regenerative medicine and pointed out the perspectives for the directions of hADSCs applications clinically. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

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12 pages, 792 KiB

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Progress and Challenges of Amniotic Fluid Derived Stem Cells in Therapy of Ischemic Heart Disease

by Yi-Hsien Fang, Saprina P. H. Wang, Hsien-Yuan Chang, Pei-Jung Yang, Ping-Yen Liu and Yen-Wen Liu

Int. J. Mol. Sci. 2021, 22(1), 102; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010102 - 24 Dec 2020

Cited by 6 | Viewed by 4733

Abstract

Cardiovascular disease is the leading cause of deaths worldwide, claiming an estimated total of 17.9 million lives each year, of which one-third of the people are under the age of 70 years. Since adult cardiomyocytes fail to regenerate, the heart loses the ability to repair itself after an injury, making patients with heart disease suffer from poor prognosis. Pluripotent stem cells have the ability to differentiate into cardiomyocytes in vitro through a well-established process, which is a new advancement in cardiac regeneration therapy. However, pluripotent stem cell-derived cardiomyocytes have certain drawbacks, such as the risk of arrhythmia and immune incompatibility. Thus, amniotic fluid stem cells (AFSCs), a relatively novel source of stem cells, have been exploited for their ability of pluripotent differentiation. In addition, since AFSCs are weakly positive for the major histocompatibility class II molecules, they may have high immune tolerance. In summary, the possibility of development of cardiomyocytes from AFSCs, as well as their transplantation in host cells to produce mechanical contraction, has been discussed. Thus, this review article highlights the progress of AFSC therapy and its application in the treatment of heart diseases in recent years. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

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26 pages, 321 KiB

Open AccessReview

Human Amniotic Epithelial Stem Cells: A Promising Seed Cell for Clinical Applications

by Chen Qiu, Zhen Ge, Wenyu Cui, Luyang Yu and Jinying Li

Int. J. Mol. Sci. 2020, 21(20), 7730; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207730 - 19 Oct 2020

Cited by 36 | Viewed by 3980

Abstract

Perinatal stem cells have been regarded as an attractive and available cell source for medical research and clinical trials in recent years. Multiple stem cell types have been identified in the human placenta. Recent advances in knowledge on placental stem cells have revealed that human amniotic epithelial stem cells (hAESCs) have obvious advantages and can be used as a novel potential cell source for cellular therapy and clinical application. hAESCs are known to possess stem-cell-like plasticity, immune-privilege, and paracrine properties. In addition, non-tumorigenicity and a lack of ethical concerns are two major advantages compared with embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). All of the characteristics mentioned above and other additional advantages, including easy accessibility and a non-invasive application procedure, make hAESCs a potential ideal cell type for use in both research and regenerative medicine in the near future. This review article summarizes current knowledge on the characteristics, therapeutic potential, clinical advances and future challenges of hAESCs in detail. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

78 pages, 3990 KiB

Open AccessReview

In Vitro Innovation of Tendon Tissue Engineering Strategies

by Maria Rita Citeroni, Maria Camilla Ciardulli, Valentina Russo, Giovanna Della Porta, Annunziata Mauro, Mohammad El Khatib, Miriam Di Mattia, Devis Galesso, Carlo Barbera, Nicholas R. Forsyth, Nicola Maffulli and Barbara Barboni

Int. J. Mol. Sci. 2020, 21(18), 6726; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186726 - 14 Sep 2020

Cited by 41 | Viewed by 7523

Abstract

Tendinopathy is the term used to refer to tendon disorders. Spontaneous adult tendon healing results in scar tissue formation and fibrosis with suboptimal biomechanical properties, often resulting in poor and painful mobility. The biomechanical properties of the tissue are negatively affected. Adult tendons have a limited natural healing capacity, and often respond poorly to current treatments that frequently are focused on exercise, drug delivery, and surgical procedures. Therefore, it is of great importance to identify key molecular and cellular processes involved in the progression of tendinopathies to develop effective therapeutic strategies and drive the tissue toward regeneration. To treat tendon diseases and support tendon regeneration, cell-based therapy as well as tissue engineering approaches are considered options, though none can yet be considered conclusive in their reproduction of a safe and successful long-term solution for full microarchitecture and biomechanical tissue recovery. In vitro differentiation techniques are not yet fully validated. This review aims to compare different available tendon in vitro differentiation strategies to clarify the state of art regarding the differentiation process. Full article

(This article belongs to the Special Issue Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges)

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