scholarly journals Comparison of advanced therapy medicinal product gingiva and skin substitutes and their in vitro wound healing potentials

2017 ◽  
Vol 12 (2) ◽  
Author(s):  
Mireille A. Boink ◽  
Sanne Roffel ◽  
Melanie Breetveld ◽  
Maria Thon ◽  
Michiel S.P. Haasjes ◽  
...  
Keyword(s):  
Wound Healing ◽  
Medicinal Product ◽  
Skin Substitutes ◽  
Advanced Therapy Medicinal Product ◽  
Advanced Therapy

scholarly journals Development of Autologous Platelet-Rich Plasma Mixed-Microfat as an Advanced Therapy Medicinal Product for Intra-Articular Injection of Radio-Carpal Osteoarthritis: From Validation Data to Preliminary Clinical Results

2019 ◽  
Vol 20 (5) ◽  
pp. 1111 ◽  
Author(s):  
Alice Mayoly ◽  
Aurélie Iniesta ◽  
Caroline Curvale ◽  
Najib Kachouh ◽  
Charlotte Jaloux ◽  
...  
Keyword(s):  
Medicinal Product ◽  
Platelet Rich Plasma ◽  
Stromal Vascular Fraction ◽  
Clinical Results ◽  
Advanced Therapy Medicinal Product ◽  
Validation Data ◽  
Painful Condition ◽  
Advanced Therapy ◽  
Functional Scores

Wrist osteoarthritis (OA) is one of the most common conditions encountered by hand surgeons with limited efficacy of non-surgical treatments. The purpose of this study is to describe the Platelet-Rich Plasma (PRP) mixed-microfat biological characteristics of an experimental Advanced Therapy Medicinal Product (ATMP) needed for clinical trial authorization and describe the clinical results obtained from our first three patients 12 months after treatment (NCT03164122). Biological characterization of microfat, PRP and mixture were analysed in vitro according to validated methods. Patients with stage four OA according to the Kellgren Lawrence classification, with failure to conservative treatment and a persistent daily painful condition >40 mm according to the visual analog scale (VAS) were treated. Microfat-PRP ATMP is a product with high platelet purity, conserved viability of stromal vascular fraction cells, chondrogenic differentiation capacity in vitro and high secretion of IL-1Ra anti-inflammatory cytokine. For patients, the only side effect was pain at the adipose tissue harvesting sites. Potential efficacy was observed with a pain decrease of over 50% (per VAS score) and the achievement of minimal clinically important differences for DASH and PRWE functional scores at one year in all three patients. Microfat-PRP ATMP presented a good safety profile after an injection in wrist OA. Efficacy trials are necessary to assess whether this innovative strategy could delay the necessity to perform non-conservative surgery.

scholarly journals Measures to minimize cross-contamination risks in Advanced Therapy Medicinal Product manufacturing

2014 ◽  
Author(s):  
Livia Roseti ◽  
Marta Serra ◽  
Brunella Grigolo
Keyword(s):  
Medicinal Product ◽  
Main Product ◽  
Good Manufacturing Practice ◽  
Cross Contamination ◽  
Medicinal Products ◽  
Advanced Therapy Medicinal Product ◽  
Advanced Therapy ◽  
European Regulations ◽  
Product Manufacturing

Current European regulations define in vitro expanded cells for clinical purposes as substantially manipulated and include them in the class of Advanced Therapy Medicinal Products to be manufactured in compliance with current Good Manufacturing Practice. These quality requirements are generally thought to be elaborate and costly. However they ensure three main product characteristics: safety, consistency and absence of cross-contamination. The term cross-contamination is used to indicate misidentification of one cell line or culture by another. The Good Manufacturing Practice Guidelines suggest some recommendations in order to prevent cross-contaminations and require a demonstration that the implemented actions are effective. Here we report some practical examples useful both to minimize cross-contamination risks in an Advanced Therapy Medicinal Product production process and to evaluate the efficacy of the adopted measures.

scholarly journals Processing and Ex Vivo Expansion of Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells for the Development of an Advanced Therapy Medicinal Product for Use in Humans

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1908
Author(s):  
Anna Labedz-Maslowska ◽  
Agnieszka Szkaradek ◽  
Tomasz Mierzwinski ◽  
Zbigniew Madeja ◽  
Ewa Zuba-Surma
Keyword(s):  
Adipose Tissue ◽  
Medicinal Product ◽  
Stromal Cells ◽  
Manufacturing Process ◽  
Cellular Therapy ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Advanced Therapy Medicinal Product ◽  
Differentiation Potential ◽  
Advanced Therapy

Adipose tissue (AT) represents a commonly used source of mesenchymal stem/stromal cells (MSCs) whose proregenerative potential has been widely investigated in multiple clinical trials worldwide. However, the standardization of the manufacturing process of MSC-based cell therapy medicinal products in compliance with the requirements of the local authorities is obligatory and will allow us to obtain the necessary permits for product administration according to its intended use. Within the research phase (RD), we optimized the protocols used for the processing and ex vivo expansion of AT-derived MSCs (AT-MSCs) for the development of an Advanced Therapy Medicinal Product (ATMP) for use in humans. Critical process parameters (including, e.g., the concentration of enzyme used for AT digestion, cell culture conditions) were identified and examined to ensure the high quality of the final product containing AT-MSCs. We confirmed the identity of isolated AT-MSCs as MSCs and their trilineage differentiation potential according to the International Society for Cellular Therapy (ISCT) recommendations. Based on the conducted experiments, in-process quality control (QC) parameters and acceptance criteria were defined for the manufacturing of hospital exemption ATMP (HE-ATMP). Finally, we conducted a validation of the manufacturing process in a GMP facility. In the current study, we presented a process approach leading to the optimization of processing and the ex vivo expansion of AT-MSCs for the development of ATMP for use in humans.

scholarly journals Temporomandibular Joint Osteoarthritis: Regenerative Treatment by a Stem Cell Containing Advanced Therapy Medicinal Product (ATMP)—An In Vivo Animal Trial

2021 ◽  
Vol 22 (1) ◽  
pp. 443
Author(s):  
Robert Köhnke ◽  
Marcus Oliver Ahlers ◽  
Moritz Alexander Birkelbach ◽  
Florian Ewald ◽  
Michael Krueger ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hyaluronic Acid ◽  
Medicinal Product ◽  
Temporomandibular Joint ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Advanced Therapy Medicinal Product ◽  
Animal Trial ◽  
Advanced Therapy ◽  
Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJ-OA) is a chronic degenerative disease that is often characterized by progressive impairment of the temporomandibular functional unit. The aim of this randomized controlled animal trial was a comparative analysis regarding the chondroregenerative potency of intra-articular stem/stromal cell therapy. Four weeks after combined mechanical and biochemical osteoarthritis induction in 28 rabbits, therapy was initiated by a single intra-articular injection, randomized into the following groups: Group 1: AB Serum (ABS); Group 2: Hyaluronic acid (HA); Group 3: Mesenchymal stromal cells (STx.); Group 4: Mesenchymal stromal cells in hyaluronic acid (HA + STx.). After another 4 weeks, the animals were euthanized, followed by histological examination of the removed joints. The histological analysis showed a significant increase in cartilage thickness in the stromal cell treated groups (HA + STx. vs. ABS, p = 0.028; HA + ST.x vs. HA, p = 0.042; STx. vs. ABS, p = 0.036). Scanning electron microscopy detected a similar heterogeneity of mineralization and tissue porosity in the subchondral zone in all groups. The single intra-articular injection of a stem cell containing, GMP-compliant advanced therapy medicinal product for the treatment of iatrogen induced osteoarthritis of the temporomandibular joint shows a chondroregenerative effect.

scholarly journals Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 778 ◽  
Author(s):  
Ruben Daum ◽  
Dmitri Visser ◽  
Constanze Wild ◽  
Larysa Kutuzova ◽  
Maria Schneider ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Cell Activation ◽  
Vascular Endothelial Cells ◽  
Endothelial Progenitor ◽  
Advanced Therapy Medicinal Product ◽  
Endothelial Colony Forming Cells ◽  
Advanced Therapy ◽  
Custom Made

Appropriate mechanical properties and fast endothelialization of synthetic grafts are key to ensure long-term functionality of implants. We used a newly developed biostable polyurethane elastomer (TPCU) to engineer electrospun vascular scaffolds with promising mechanical properties (E-modulus: 4.8 ± 0.6 MPa, burst pressure: 3326 ± 78 mmHg), which were biofunctionalized with fibronectin (FN) and decorin (DCN). Neither uncoated nor biofunctionalized TPCU scaffolds induced major adverse immune responses except for minor signs of polymorph nuclear cell activation. The in vivo endothelial progenitor cell homing potential of the biofunctionalized scaffolds was simulated in vitro by attracting endothelial colony-forming cells (ECFCs). Although DCN coating did attract ECFCs in combination with FN (FN + DCN), DCN-coated TPCU scaffolds showed a cell-repellent effect in the absence of FN. In a tissue-engineering approach, the electrospun and biofunctionalized tubular grafts were cultured with primary-isolated vascular endothelial cells in a custom-made bioreactor under dynamic conditions with the aim to engineer an advanced therapy medicinal product. Both FN and FN + DCN functionalization supported the formation of a confluent and functional endothelial layer.

scholarly journals Are the Immune Properties of Mesenchymal Stem Cells from Wharton’s Jelly Maintained during Chondrogenic Differentiation?

2020 ◽  
Vol 9 (2) ◽  
pp. 423 ◽  
Author(s):  
Charlotte Voisin ◽  
Ghislaine Cauchois ◽  
Loïc Reppel ◽  
Caroline Laroye ◽  
Laetitia Louarn ◽  
...  
Keyword(s):  
Chondrogenic Differentiation ◽  
Immunological Synapse ◽  
Wharton’S Jelly ◽  
Chondrocyte Differentiation ◽  
Advanced Therapy Medicinal Product ◽  
Wharton's Jelly ◽  
Advanced Therapy ◽  
Tnf Α ◽  
Ifn Γ

Background: Umbilical mesenchymal stem/stromal cells (MSCs), and especially those derived from Wharton’s jelly (WJ), are a promising engineering tool for tissue repair in an allogeneic context. This is due to their differentiation capacity and immunological properties, like their immunomodulatory potential and paracrine activity. Hence, these cells may be considered an Advanced Therapy Medicinal Product (ATMP). The purpose of this work was to differentiate MSCs from WJ (WJ-MSCs) into chondrocytes using a scaffold and to evaluate, in vitro, the immunomodulatory capacities of WJ-MSCs in an allogeneic and inflammatory context, mimicked by IFN-γ and TNF-α priming during the chondrogenic differentiation. Methods: Scaffolds were made from hydrogel composed by alginate enriched in hyaluronic acid (Alg/HA). Chondrogenic differentiation, immunological function, phenotype expression, but also secreted soluble factors were the different parameters followed during 28 days of culture. Results: During chondrocyte differentiation, even in an allogeneic context, WJ-MSCs remained unable to establish the immunological synapse or to induce T cell alloproliferation. Moreover, interestingly, paracrine activity and functional immunomodulation were maintained during cell differentiation. Conclusion: These results show that WJ-MSCs remained hypoimmunogenic and retained immunomodulatory properties even when they had undergone chondrocyte differentiation.

scholarly journals Advanced therapy medicinal product manufacturing under the hospital exemption and other exemption pathways in seven European Union countries

Cytotherapy ◽  
2020 ◽  
Vol 22 (10) ◽  
pp. 592-600
Author(s):  
Delphi G.M. Coppens ◽  
Jarno Hoekman ◽  
Marie L. De Bruin ◽  
Ineke C.M. Slaper-Cortenbach ◽  
Hubert G.M. Leufkens ◽  
...  
Keyword(s):  
European Union ◽  
Medicinal Product ◽  
Advanced Therapy Medicinal Product ◽  
Advanced Therapy ◽  
European Union Countries ◽  
Product Manufacturing
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