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Biomedicines
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Advanced Research in Stem Cells and Regenerative Medicine
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Advanced Research in Stem Cells and Regenerative Medicine

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 10430

Special Issue Editors

Prof. Dr. Roberta Di Pietro

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Guest Editor
Department of Medicine and Ageing Sciences, G. d’Annunzio University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
Interests: ageing; cell signaling; cell death; apoptosis; TRAIL; CREB; ionizing radiation; hematological malignancies; pterygium; pancreas adenocarcinoma; cell differentiation; stem cells; amniotic membrane; placenta; regenerative medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Sandra Marmiroli

E-Mail Website
Guest Editor
Department of Biomedical, Metabolic and Neuronal Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Interests: cellular signaling; lipid-activated protein kinases; identification of isoform-specific substrates of the AKT protein kinase; modulation of glycolytic vs. oxidative cellular phenotypes by signaling pathways in acute leukemia models; definition of the phosphorylome of primary blast cells from leukemia patients, and its modulation by the PI3K pathway; kinase-inhibitor therapy in hematological malignancies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stem cells are a population of undifferentiated cells characterized by their ability to extensively proliferate (self-renewal) and differentiate into different cell types (potency). There are several sources of stem cells with varying potencies. In recent years, increasing attention has been paid to perinatal derivatives due to the absence of ethical issues, since they are discarded after childbirth. Many preclinical studies and initial clinical trials have demonstrated that perinatal derivatives may represent important tools for restoring tissue damage or promoting regeneration and repair of the tissue microenvironment.

This Special Issue welcomes all types of manuscripts providing insight on aspects relevant to the use of perinatal derivatives in regenerative medicine. We are interested in a wide range of work, including differentiation to novel cell types or improvement on existing cell types, as well as their preclinical testing. Moreover, we are interested in understanding endogenous processes of tissue repair and homeostasis, stem cells’ biology in relation to their therapeutic potential, new approaches in the tracking and imaging of both stem cells and tissues/organs undergoing regeneration, and data from clinical trials of stem-cell-based therapies. Finally, the mechanisms of stem cells’ activity, including secretome and extracellular vesicles production, will be highly appreciated.

Prof. Dr. Roberta Di Pietro
Prof. Dr. Sandra Marmiroli
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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • stem cells
  • tissue homeostasis and repair
  • cell renewal
  • morphogenesis
  • embryo development
  • regenerative medicine
  • stem cell differentiation
  • homing
  • signaling in the stem cell niche
  • perinatal derivatives
  • secretome
  • extracellular vesicles

Published Papers (6 papers)

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14 pages, 8420 KiB  
Article
Processing Adipose Tissue Samples in a GMP Environment Standardizes the Use of SVF in Cell Therapy Treatments: Data on 302 Patients
by Martina Cremona, Giulio Rusconi, Alessandro Ferrario, Luca Mariotta, Mauro Gola and Gianni Soldati
Biomedicines 2023, 11(9), 2533; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11092533 - 14 Sep 2023
Viewed by 974
Abstract
Stromal vascular fraction (SVF) cells, together with adipose-derived mesenchymal stem cells, are becoming the tool of choice for many clinical applications. Currently, nearly 200 clinical trials are running worldwide to prove the efficacy of this cell type in treating many diseases and pathological [...] Read more.
Stromal vascular fraction (SVF) cells, together with adipose-derived mesenchymal stem cells, are becoming the tool of choice for many clinical applications. Currently, nearly 200 clinical trials are running worldwide to prove the efficacy of this cell type in treating many diseases and pathological conditions. To reach the goals of cell therapies and produce ATMPs as drugs for regenerative medicine, it is necessary to properly standardize GMP processes and, thus, collection methods, transportation strategies, extraction protocols, and characterization procedures, without forgetting that all the tissues of the human body are characterized by a wide inter-individual variability which is genetically determined and acquired during life. Here, we compare 302 samples processed under GMP rules to exclude the influence of the operator and of the anatomical site of collection. The influence of variability in the ages and genders of patients, along with laboratory parameters such as total cell number, cell viability, stem cell number, and other stromal vascular fraction cell subpopulations, has been compared. The results show that when the laboratory protocol is standardized, the variability of quantifiable cell parameters is widely statistically non-significant, meaning that we can take a further step toward standardized advanced cell therapy products. Full article
(This article belongs to the Special Issue Advanced Research in Stem Cells and Regenerative Medicine)
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17 pages, 16356 KiB  
Article
A Novel Benchtop Device for Efficient and Simple Purification of Cytokines, Growth Factors and Stem Cells from Adipose Tissue
by Martina Semenzato, Ludovica Zambello, Stefania Fumarola, Enrico Motta, Luana Piroli, Luca Scorrano and Camilla Bean
Biomedicines 2023, 11(4), 1006; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11041006 - 24 Mar 2023
Viewed by 1641
Abstract
Lipoaspirates represent a source of adult stem cells, cytokines, and growth factors of adipocyte origin with immunomodulation and regenerative medicine potential. However, rapid and simple protocols for their purification using self-contained devices that can be deployed at the points of care are lacking. [...] Read more.
Lipoaspirates represent a source of adult stem cells, cytokines, and growth factors of adipocyte origin with immunomodulation and regenerative medicine potential. However, rapid and simple protocols for their purification using self-contained devices that can be deployed at the points of care are lacking. Here, we characterize and benchmark a straightforward mechanical dissociation procedure to collect mesenchymal stem cells (MSCs) and soluble fractions from lipoaspirates. IStemRewind, a benchtop self-contained cell purification device, allowed a one-procedure purification of cells and soluble material from lipoaspirates with minimal manipulation. The recovered cellular fraction contained CD73+, CD90+, CD105+, CD10+ and CD13+ MSCs. These markers were comparably expressed on MSCs isolated using IstemRewind or classic enzymatic dissociation procedures, apart from CD73+ MSCs, which were even more abundant in IStemRewind isolates. IstemRewind-purified MSCs retained viability and differentiation into adipocytes and osteocytes, even after a freezing-thawing cycle. Levels of IL4, IL10, bFGF and VEGF were higher compared to the pro-inflammatory cytokines TNFα, IL1β and IL6 in the IStemRewind-isolated liquid fraction. In sum, IStemRewind can be useful for straightforward, rapid, and efficient isolation of MSCs and immunomodulatory soluble factors from lipoaspirates, opening the possibility to directly isolate and employ them at the point-of-care. Full article
(This article belongs to the Special Issue Advanced Research in Stem Cells and Regenerative Medicine)
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16 pages, 4116 KiB  
Article
Effect of the Enrichment in c-Kit Stem Cell Potential of Foetal Human Amniotic Fluid Cells: Characterization from Single Cell Analysis to the Secretome Content
by Francesca Casciaro, Francesca Beretti, Martina Gatti, Giuseppe Persico, Emma Bertucci, Marco Giorgio and Tullia Maraldi
Biomedicines 2023, 11(2), 430; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11020430 - 02 Feb 2023
Viewed by 1617
Abstract
Human amniotic fluid cells (hAFSCs) are a fascinating foetal cell-type that have important stem cell characteristics; however, they are a heterogeneous population that ranges from totally differentiated or progenitor cells to highly multipotent stem cells. There is no single approach to isolating the [...] Read more.
Human amniotic fluid cells (hAFSCs) are a fascinating foetal cell-type that have important stem cell characteristics; however, they are a heterogeneous population that ranges from totally differentiated or progenitor cells to highly multipotent stem cells. There is no single approach to isolating the stem cell component, but the selection of a subpopulation of hAFSCs expressing c-Kit is widely employed, while a deep characterization of the two populations is still lacking. Here we performed single-cell and bulk RNAseq analysis to compare the gene expression profiles of adherent amniotic fluid cells and their subpopulation c-Kit+. Information deriving from this high throughput technology on the transcriptome was then confirmed for specific targets with protein expression experiments and functional analysis. In particular, transcriptome profiling identified changes in cellular distribution among the different clusters that correlated with significant differential expression in pathways related to stemness, proliferation, and cell cycle checkpoints. These differences were validated by RT-PCR, immunofluorescence, WB, and cell cycle assays. Interestingly, the two populations produced secretomes with different immune-modulating and pro-regenerative potentials. Indeed, the presence of TGFβ, HGF, IDO was higher in EVs deriving from c-Kit+ cells, unlike IL-6. These results suggest the existence of deep intra-population differences that can influence the stemness profile of hAFSCs. This study represents a proof-of-concept of the importance of selecting c-Kit positive fractions with higher potential in regenerative medicine applications. Full article
(This article belongs to the Special Issue Advanced Research in Stem Cells and Regenerative Medicine)
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30 pages, 12877 KiB  
Article
Tendon Healing Response Is Dependent on Epithelial–Mesenchymal–Tendon Transition State of Amniotic Epithelial Stem Cells
by Valentina Russo, Annunziata Mauro, Alessia Peserico, Oriana Di Giacinto, Mohammad El Khatib, Maria Rita Citeroni, Emanuela Rossi, Angelo Canciello, Eleonora Mazzotti and Barbara Barboni
Biomedicines 2022, 10(5), 1177; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051177 - 19 May 2022
Cited by 7 | Viewed by 1855
Abstract
Tendinopathies are at the frontier of advanced responses to health challenges and sectoral policy targets. Cell-based therapy holds great promise for tendon disorder resolution. To verify the role of stepwise trans-differentiation of amniotic epithelial stem cells (AECs) in tendon regeneration, in the present [...] Read more.
Tendinopathies are at the frontier of advanced responses to health challenges and sectoral policy targets. Cell-based therapy holds great promise for tendon disorder resolution. To verify the role of stepwise trans-differentiation of amniotic epithelial stem cells (AECs) in tendon regeneration, in the present research three different AEC subsets displaying an epithelial (eAECs), mesenchymal (mAECs), and tendon-like (tdAECs) phenotype were allotransplanted in a validated experimental sheep Achilles tendon injury model. Tissue healing was analyzed adopting a comparative approach at two early healing endpoints (14 and 28 days). All three subsets of transplanted cells were able to accelerate regeneration: mAECs with a lesser extent than eAECs and tdAECs as indicated in the summary of the total histological scores (TSH), where at day 28 eAECs and tdAECs had better significant scores with respect to mAEC-treated tendons (p < 0.0001). In addition, the immunomodulatory response at day 14 showed in eAEC-transplanted tendons an upregulation of pro-regenerative M2 macrophages with respect to mAECs and tdAECs (p < 0.0001). In addition, in all allotransplanted tendons there was a favorable IL10/IL12 compared to CTR (p < 0.001). The eAECs and tdAECs displayed two different underlying regenerative mechanisms in the tendon. The eAECs positively influenced regeneration mainly through their greater ability to convey in the host tissue the shift from pro-inflammatory to pro-regenerative responses, leading to an ordered extracellular matrix (ECM) deposition and blood vessel remodeling. On the other hand, the transplantation of tdAECs acted mainly on the proliferative phase by impacting the density of ECM and by supporting a prompt recovery, inducing a low cellularity and angle alignment of the host cell compartment. These results support the idea that AECs lay the groundwork for production of different cell phenotypes that can orient tendon regeneration through a crosstalk with the host tissue. In particular, the obtained evidence suggests that eAECs are a practicable and efficient strategy for the treatment of acute tendinopathies, thus reinforcing the grounds to move their use towards clinical practice. Full article
(This article belongs to the Special Issue Advanced Research in Stem Cells and Regenerative Medicine)
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20 pages, 986 KiB  
Systematic Review
Platelet Rich Plasma and Platelet-Related Products in the Treatment of Radiculopathy—A Systematic Review of the Literature
by Eva Kubrova, Gabriel A. Martinez Alvarez, Yeng F. Her, Robert Pagan-Rosado, Wenchun Qu and Ryan S. D’Souza
Biomedicines 2022, 10(11), 2813; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10112813 - 04 Nov 2022
Cited by 4 | Viewed by 2134
Abstract
Back pain with radicular symptoms is associated with detrimental physical and emotional functioning and economic burden. Conservative treatments including physical, pharmacologic and injection therapy may not provide clinically significant or long-standing relief. Regenerative medicine research including Platelet rich plasma (PRP), Platelet lysate (PL) [...] Read more.
Back pain with radicular symptoms is associated with detrimental physical and emotional functioning and economic burden. Conservative treatments including physical, pharmacologic and injection therapy may not provide clinically significant or long-standing relief. Regenerative medicine research including Platelet rich plasma (PRP), Platelet lysate (PL) or Plasma rich in growth factors (PRGF) continues to develop, however evidence appraisal for treatment of radicular pain remains lacking. Thus, we performed a systematic review to evaluate the effectiveness of epidural steroid injections containing PRP or related products to treat radicular pain. Embase, PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were queried. Twelve studies were included in qualitative analysis, consisting of three randomized controlled trials and nine observational studies. The primary outcome was pain intensity, and secondary outcomes included functional improvement, anatomical changes on advanced imaging, and adverse events. All studies identified improved pain intensity and functional outcomes after epidural injection of PRP, PRGF and/or PL. Similar or longer lasting pain relief was noted in the PRP cohort compared to the cohort receiving epidural steroid injections with effects lasting up to 12–24 months. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis revealed a very-low certainty of evidence due to risk of bias, indirectness, and imprecision. Full article
(This article belongs to the Special Issue Advanced Research in Stem Cells and Regenerative Medicine)
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5 pages, 240 KiB  
Opinion
Questions about Residual Cell Viability in Cryopreserved Human Amniotic Membrane and Its Impact on Clinical Applications
by Camille Gaudet, Lauriana Solecki, Bastien Mathéaud, Stephane Odet, Christophe Meyer, Aurélien Louvrier and Florelle Gindraux
Biomedicines 2022, 10(10), 2456; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10102456 - 01 Oct 2022
Cited by 1 | Viewed by 1162
Abstract
We questioned the relevance of evaluating residual cell viability in human amniotic membrane (hAM) after its cryopreservation since cell survival is controversial and its ability to act as a matrix (including the presence of growth factors and cytokines) appears to be most important [...] Read more.
We questioned the relevance of evaluating residual cell viability in human amniotic membrane (hAM) after its cryopreservation since cell survival is controversial and its ability to act as a matrix (including the presence of growth factors and cytokines) appears to be most important for tissue regeneration purposes. We also discussed the usefulness of osteodifferentiating amniotic cells in whole hAM for bone repair applications. We have evidence that determining residual cell viability after cryopreservation and hAM osteodifferentiation is not justified. Full article
(This article belongs to the Special Issue Advanced Research in Stem Cells and Regenerative Medicine)
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