Where Are We Now and Where Is Cell Therapy Headed?

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: 30 October 2024 | Viewed by 5683

Special Issue Editors


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Guest Editor
Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Interests: immunomodulation; mesenchymal stromal cells; cancer biology; regenerative medicine; immunology; perinatal derivatives; secretoma; extracellular vesicles
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Interests: angiogenesis; cancer biology; spheroids; mesenchymal stromal cells; cancer associated fibroblasts; perinatal derivatives
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cell therapy has experienced both significant achievements and setbacks to date. Despite this, cell therapy continues to be a cutting-edge approach to the treatment of many illnesses for which there are no pharmaceutical alternatives at present. However, as with other areas of knowledge, the situation is continuously changing and follows the trend of technological advancements. What was once regarded as cell transplantation is now giving way to new horizons such as the use of the cell secretome, or constituents thereof, such as extracellular vesicles.

For this Special Issue, we invite renowned scientists to contribute their original research and review articles to advance the understanding of the applications of stem cells and mesenchymal stromal cells in health and disease, as well as how these could be exploited for therapeutic purposes.

Possible subjects include, but are not limited to:

  • Research on the therapeutic translation of mesenchymal stromal cells, stem cells, and their byproducts (e.g., secretome, extracellular vesicles);
  • Research on disease models that can explain how altered stem niches affect disease etiology;
  • Cell and gene therapy approaches for the treatment of diseases;
  • The use of CAR-T and CAR-NK cells for the treatment of leukemia and solid tumors;
  • The application of genetically modified MSC or of MSC to deliver drug cargoes for the treatment of cancer.

Dr. Andrea Papait
Dr. Paola Chiodelli
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 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
  • mesenchymal stromal cells
  • cell therapy
  • CAR-T
  • CAR-NK
  • cancer
  • gene therapy
  • organoids and organ on a chip
  • extracellular vesicles
  • secretome

Published Papers (4 papers)

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Research

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25 pages, 21282 KiB  
Article
Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care
by Xi Chen, Alexis Laurent, Zhifeng Liao, Sandra Jaccoud, Philippe Abdel-Sayed, Marjorie Flahaut, Corinne Scaletta, Wassim Raffoul, Lee Ann Applegate and Nathalie Hirt-Burri
Pharmaceutics 2023, 15(9), 2334; https://doi.org/10.3390/pharmaceutics15092334 - 16 Sep 2023
Cited by 2 | Viewed by 1004
Abstract
Autologous cell therapy manufacturing timeframes constitute bottlenecks in clinical management pathways of severe burn patients. While effective temporary wound coverings exist for high-TBSA burns, any means to shorten the time-to-treatment with cytotherapeutic skin grafts could provide substantial therapeutic benefits. This study aimed to [...] Read more.
Autologous cell therapy manufacturing timeframes constitute bottlenecks in clinical management pathways of severe burn patients. While effective temporary wound coverings exist for high-TBSA burns, any means to shorten the time-to-treatment with cytotherapeutic skin grafts could provide substantial therapeutic benefits. This study aimed to establish proofs-of-concept for a novel combinational cytotherapeutic construct (autologous/allogeneic DE-FE002-SK2 full dermo-epidermal graft) designed for significant cutaneous cell therapy manufacturing timeframe rationalization. Process development was based on several decades (four for autologous protocols, three for allogeneic protocols) of in-house clinical experience in cutaneous cytotherapies. Clinical grade dermal progenitor fibroblasts (standardized FE002-SK2 cell source) were used as off-the-freezer substrates in novel autologous/allogeneic dermo-epidermal bilayer sheets. Under vitamin C stimulation, FE002-SK2 primary progenitor fibroblasts rapidly produced robust allogeneic dermal templates, allowing patient keratinocyte attachment in co-culture. Notably, FE002-SK2 primary progenitor fibroblasts significantly outperformed patient fibroblasts for collagen deposition. An ex vivo de-epidermalized dermis model was used to demonstrate the efficient DE-FE002-SK2 construct bio-adhesion properties. Importantly, the presented DE-FE002-SK2 manufacturing process decreased clinical lot production timeframes from 6–8 weeks (standard autologous combined cytotherapies) to 2–3 weeks. Overall, these findings bear the potential to significantly optimize burn patient clinical pathways (for rapid wound closure and enhanced tissue healing quality) by combining extensively clinically proven cutaneous cell-based technologies. Full article
(This article belongs to the Special Issue Where Are We Now and Where Is Cell Therapy Headed?)
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33 pages, 20827 KiB  
Article
Autologous and Allogeneic Cytotherapies for Large Knee (Osteo)Chondral Defects: Manufacturing Process Benchmarking and Parallel Functional Qualification
by Virginie Philippe, Annick Jeannerat, Cédric Peneveyre, Sandra Jaccoud, Corinne Scaletta, Nathalie Hirt-Burri, Philippe Abdel-Sayed, Wassim Raffoul, Salim Darwiche, Lee Ann Applegate, Robin Martin and Alexis Laurent
Pharmaceutics 2023, 15(9), 2333; https://doi.org/10.3390/pharmaceutics15092333 - 16 Sep 2023
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Abstract
Cytotherapies are often necessary for the management of symptomatic large knee (osteo)-chondral defects. While autologous chondrocyte implantation (ACI) has been clinically used for 30 years, allogeneic cells (clinical-grade FE002 primary chondroprogenitors) have been investigated in translational settings (Swiss progenitor cell transplantation program). The [...] Read more.
Cytotherapies are often necessary for the management of symptomatic large knee (osteo)-chondral defects. While autologous chondrocyte implantation (ACI) has been clinically used for 30 years, allogeneic cells (clinical-grade FE002 primary chondroprogenitors) have been investigated in translational settings (Swiss progenitor cell transplantation program). The aim of this study was to comparatively assess autologous and allogeneic approaches (quality, safety, functional attributes) to cell-based knee chondrotherapies developed for clinical use. Protocol benchmarking from a manufacturing process and control viewpoint enabled us to highlight the respective advantages and risks. Safety data (telomerase and soft agarose colony formation assays, high passage cell senescence) and risk analyses were reported for the allogeneic FE002 cellular active substance in preparation for an autologous to allogeneic clinical protocol transposition. Validation results on autologous bioengineered grafts (autologous chondrocyte-bearing Chondro-Gide scaffolds) confirmed significant chondrogenic induction (COL2 and ACAN upregulation, extracellular matrix synthesis) after 2 weeks of co-culture. Allogeneic grafts (bearing FE002 primary chondroprogenitors) displayed comparable endpoint quality and functionality attributes. Parameters of translational relevance (transport medium, finished product suturability) were validated for the allogeneic protocol. Notably, the process-based benchmarking of both approaches highlighted the key advantages of allogeneic FE002 cell-bearing grafts (reduced cellular variability, enhanced process standardization, rationalized logistical and clinical pathways). Overall, this study built on our robust knowledge and local experience with ACI (long-term safety and efficacy), setting an appropriate standard for further clinical investigations into allogeneic progenitor cell-based orthopedic protocols. Full article
(This article belongs to the Special Issue Where Are We Now and Where Is Cell Therapy Headed?)
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39 pages, 11341 KiB  
Article
Bio-Enhanced Neoligaments Graft Bearing FE002 Primary Progenitor Tenocytes: Allogeneic Tissue Engineering & Surgical Proofs-of-Concept for Hand Ligament Regenerative Medicine
by Annick Jeannerat, Joachim Meuli, Cédric Peneveyre, Sandra Jaccoud, Michèle Chemali, Axelle Thomas, Zhifeng Liao, Philippe Abdel-Sayed, Corinne Scaletta, Nathalie Hirt-Burri, Lee Ann Applegate, Wassim Raffoul and Alexis Laurent
Pharmaceutics 2023, 15(7), 1873; https://doi.org/10.3390/pharmaceutics15071873 - 3 Jul 2023
Viewed by 1227
Abstract
Hand tendon/ligament structural ruptures (tears, lacerations) often require surgical reconstruction and grafting, for the restauration of finger mechanical functions. Clinical-grade human primary progenitor tenocytes (FE002 cryopreserved progenitor cell source) have been previously proposed for diversified therapeutic uses within allogeneic tissue engineering and regenerative [...] Read more.
Hand tendon/ligament structural ruptures (tears, lacerations) often require surgical reconstruction and grafting, for the restauration of finger mechanical functions. Clinical-grade human primary progenitor tenocytes (FE002 cryopreserved progenitor cell source) have been previously proposed for diversified therapeutic uses within allogeneic tissue engineering and regenerative medicine applications. The aim of this study was to establish bioengineering and surgical proofs-of-concept for an artificial graft (Neoligaments Infinity-Lock 3 device) bearing cultured and viable FE002 primary progenitor tenocytes. Technical optimization and in vitro validation work showed that the combined preparations could be rapidly obtained (dynamic cell seeding of 105 cells/cm of scaffold, 7 days of co-culture). The studied standardized transplants presented homogeneous cellular colonization in vitro (cellular alignment/coating along the scaffold fibers) and other critical functional attributes (tendon extracellular matrix component such as collagen I and aggrecan synthesis/deposition along the scaffold fibers). Notably, major safety- and functionality-related parameters/attributes of the FE002 cells/finished combination products were compiled and set forth (telomerase activity, adhesion and biological coating potentials). A two-part human cadaveric study enabled to establish clinical protocols for hand ligament cell-assisted surgery (ligamento-suspension plasty after trapeziectomy, thumb metacarpo-phalangeal ulnar collateral ligamentoplasty). Importantly, the aggregated experimental results clearly confirmed that functional and clinically usable allogeneic cell-scaffold combination products could be rapidly and robustly prepared for bio-enhanced hand ligament reconstruction. Major advantages of the considered bioengineered graft were discussed in light of existing clinical protocols based on autologous tenocyte transplantation. Overall, this study established proofs-of-concept for the translational development of a functional tissue engineering protocol in allogeneic musculoskeletal regenerative medicine, in view of a pilot clinical trial. Full article
(This article belongs to the Special Issue Where Are We Now and Where Is Cell Therapy Headed?)
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Review

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22 pages, 1578 KiB  
Review
Therapies Targeting Immune Cells in Tumor Microenvironment for Non-Small Cell Lung Cancer
by Wei Ye, Meiye Li and Kewang Luo
Pharmaceutics 2023, 15(7), 1788; https://doi.org/10.3390/pharmaceutics15071788 - 21 Jun 2023
Cited by 3 | Viewed by 1596
Abstract
The tumor microenvironment (TME) plays critical roles in immune modulation and tumor malignancies in the process of cancer development. Immune cells constitute a significant component of the TME and influence the migration and metastasis of tumor cells. Recently, a number of therapeutic approaches [...] Read more.
The tumor microenvironment (TME) plays critical roles in immune modulation and tumor malignancies in the process of cancer development. Immune cells constitute a significant component of the TME and influence the migration and metastasis of tumor cells. Recently, a number of therapeutic approaches targeting immune cells have proven promising and have already been used to treat different types of cancer. In particular, PD-1 and PD-L1 inhibitors have been used in the first-line setting in non-small cell lung cancer (NSCLC) with PD-L1 expression ≥1%, as approved by the FDA. In this review, we provide an introduction to the immune cells in the TME and their efficacies, and then we discuss current immunotherapies in NSCLC and scientific research progress in this field. Full article
(This article belongs to the Special Issue Where Are We Now and Where Is Cell Therapy Headed?)
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