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Advanced Therapy Medicinal Products: From Mechanism to Production
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Advanced Therapy Medicinal Products: From Mechanism to Production

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 7700

Special Issue Editor

Dr. Massimiliano Petrini

E-Mail Website
Guest Editor
Osteoncology and Rare Tumors Center, Immunotherapy, Cell Therapy and Biobank, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
Interests: dendritic cells; advanced therapy medicinal products; TIL; quality control test; flow cytometry; potency test; GMP regulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Advanced therapy medicinal products (ATMPs), based on genetically modified genes, tissues, or cells, are the most promising innovative medicines at the moment.

Traditional pre-clinical tests are often not appropriate for assessing the safety of gene and cell therapy products and may not be able to detect effects relevant to human efficacy and safety.

For this, it is particularly important to understand and study functional mechanisms, toxicity, and persistence capacity.

It is also crucial to develop new in vitro potency tests that can predict therapeutic effects, and to discover predictive response factors.

Another issue is the standardization and the safety of the production process in agreement with regulatory authorities rules in order to reduce costs and universalize these therapies.

In this Special Issue, we invite contributions in the form of original research articles, reviews, or shorter perspective articles on all aspects related to ATMPS and the themes listed above.

Dr. Massimiliano Petrini
Guest Editor

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.

Published Papers (3 papers)

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Research

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15 pages, 2116 KiB  
Article
Controlling Macrophage Polarization to Modulate Inflammatory Cues Using Immune-Switch Nanoparticles
by Ana F. Almeida, Margarida S. Miranda, Adriana Vinhas, Ana I. Gonçalves, Manuela E. Gomes and Márcia T. Rodrigues
Int. J. Mol. Sci. 2022, 23(23), 15125; https://doi.org/10.3390/ijms232315125 - 1 Dec 2022
Cited by 1 | Viewed by 1791
Abstract
The persistence of inflammatory mediators in tissue niches significantly impacts regenerative outcomes and contributes to chronic diseases. Interleukin-4 (IL4) boosts pro-healing phenotypes in macrophages (Mφ) and triggers the activation of signal transducer and activator of transcription 6 (STAT6). Since the IL4/STAT6 pathway reduces [...] Read more.
The persistence of inflammatory mediators in tissue niches significantly impacts regenerative outcomes and contributes to chronic diseases. Interleukin-4 (IL4) boosts pro-healing phenotypes in macrophages (Mφ) and triggers the activation of signal transducer and activator of transcription 6 (STAT6). Since the IL4/STAT6 pathway reduces Mφ responsiveness to inflammation in a targeted and precise manner, IL4 delivery offers personalized possibilities to overcome inflammatory events. Despite its therapeutic potential, the limited success of IL4-targeted delivery is hampered by inefficient vehicles. Magnetically assisted technologies offer precise and tunable nanodevices for the delivery of cytokines by combining contactless modulation, high tissue penetration, imaging features, and low interference with the biological environment. Although superparamagnetic iron oxide nanoparticles (SPION) have shown clinical applicability in imaging, SPION-based approaches have rarely been explored for targeted delivery and cell programming. Herein, we hypothesized that SPION-based carriers assist in efficient IL4 delivery to Mφ, favoring a pro-regenerative phenotype (M2φ). Our results confirmed the efficiency of SPION-IL4 and Mφ responsiveness to SPION-IL4 with evidence of STAT6-mediated polarization. SPION-IL4-treated Mφ showed increased expression of M2φ associated-mediators (IL10, ARG1, CCL2, IL1Ra) when compared to the well-established soluble IL4. The ability of SPION-IL4 to direct Mφ polarization using sophisticated magnetic nanotools is valuable for resolving inflammation and assisting innovative strategies for chronic inflammatory conditions. Full article
(This article belongs to the Special Issue Advanced Therapy Medicinal Products: From Mechanism to Production)
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17 pages, 2749 KiB  
Article
Human Mesenchymal Stem Cell Secretome Driven T Cell Immunomodulation Is IL-10 Dependent
by Matthew T. Shephard, Marwan M. Merkhan and Nicholas R. Forsyth
Int. J. Mol. Sci. 2022, 23(21), 13596; https://doi.org/10.3390/ijms232113596 - 6 Nov 2022
Cited by 35 | Viewed by 2229
Abstract
The Human Mesenchymal Stem Cell (hMSC) secretome has pleiotropic effects underpinning its therapeutic potential. hMSC serum-free conditioned media (SFCM) contains a variety of cytokines, with previous studies linking a changed secretome composition to physoxia. The Jurkat T cell model allowed the efficacy of [...] Read more.
The Human Mesenchymal Stem Cell (hMSC) secretome has pleiotropic effects underpinning its therapeutic potential. hMSC serum-free conditioned media (SFCM) contains a variety of cytokines, with previous studies linking a changed secretome composition to physoxia. The Jurkat T cell model allowed the efficacy of SFCM vs. serum-free media (SFM) in the suppression of immunological aspects, including proliferation and polarisation, to be explored. Cell growth in SFM was higher [(21% O2 = 5.3 × 105 ± 1.8 × 104 cells/mL) and (2% O2 = 5.1 × 105 ± 3.0 × 104 cells/mL)], compared to SFCM [(21% O2 = 2.4 × 105 ± 2.5 × 104 cells/mL) and (2% O2 = 2.2 × 105 ± 5.8 × 103 cells/mL)]. SFM supported IL-2 release following activation [(21% O2 = 5305 ± 211 pg/mL) and (2% O2 = 5347 ± 327 pg/mL)] whereas SFCM suppressed IL-2 secretion [(21% O2 = 2461 ± 178 pg/mL) and (2% O2 = 1625 ± 159 pg/mL)]. Anti-inflammatory cytokines, namely IL-4, IL-10, and IL-13, which we previously confirmed as components of hMSC SFCM, were tested. IL-10 neutralisation in SFCM restored proliferation in both oxygen environments (SFM/SFCM+antiIL−10 ~1-fold increase). Conversely, IL-4/IL-13 neutralisation showed no proliferation restoration [(SFM/SFM+antiIL−4 ~2-fold decrease), and (SFM/SFCM+antiIL−13 ~2-fold decrease)]. Present findings indicate IL-10 played an immunosuppressive role by reducing IL-2 secretion. Identification of immunosuppressive components of the hMSC secretome and a mechanistic understanding of their action allow for the advancement and refinement of potential future cell-free therapies. Full article
(This article belongs to the Special Issue Advanced Therapy Medicinal Products: From Mechanism to Production)
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Review

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28 pages, 4721 KiB  
Review
Hyaluronic Acid in Biomedical Fields: New Trends from Chemistry to Biomaterial Applications
by Antonia Di Mola, Maria Rosaria Landi, Antonio Massa, Ugo D’Amora and Vincenzo Guarino
Int. J. Mol. Sci. 2022, 23(22), 14372; https://doi.org/10.3390/ijms232214372 - 19 Nov 2022
Cited by 18 | Viewed by 3158
Abstract
The aim of this review is to give an updated perspective about the methods for chemical modifications of hyaluronic acid (HA) toward the development of new applications in medical devices and material engineering. After a brief introduction on chemical, structural and biological features [...] Read more.
The aim of this review is to give an updated perspective about the methods for chemical modifications of hyaluronic acid (HA) toward the development of new applications in medical devices and material engineering. After a brief introduction on chemical, structural and biological features of this important natural polysaccharide, the most important methods for chemical and physical modifications are disclosed, discussing both on the formation of new covalent bonds and the interaction with other natural polysaccharides. These strategies are of paramount importance in the production of new medical devices and materials with improved properties. In particular, the use of HA in the development of new materials by means of additive manufacturing techniques as electro fluid dynamics, i.e., electrospinning for micro to nanofibres, and three-dimensional bioprinting is also discussed. Full article
(This article belongs to the Special Issue Advanced Therapy Medicinal Products: From Mechanism to Production)
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