First-in-human PeriCord cardiac bioimplant: Scalability and GMP manufacturing of an allogeneic engineered tissue graft

Prat‐Vidal, Cristina; Rodríguez-Gómez, Luciano; Aylagas, Miriam; Nieto‐Nicolau, Núria; Gastelurrutia, Paloma; Agustí, Elba; Gálvez‐Montón, Carolina; Jorba, Ignasi; Teis, Albert; Monguió‐Tortajada, Marta; Roura, Santiago; Vives, Joaquim; Torrents-Zapata, S.; Coca, María Isabel; Reales, Laura; Cámara-Rosell, María Luisa; Cediel, Germán; Coll, Ruth; Farré, Ramón; Navajas, Daniel; Vilarrodona, Anna; García‐López, Joan; Muñoz-Guijosa, Christian; Querol, Sergi; Bayés‐Genís, Antoni

doi:10.1016/j.ebiom.2020.102729

Cited by 33 publications

(33 citation statements)

References 35 publications

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“…In this context, decellularised cardiac scaffolds are a source of biological ECM derived from native cardiac tissues, with conserved micro- and macro-scale ECM structure and functional cardiac ECM composition [ 32 , 33 ]. Specifically, we already have a protocol approved by the Spanish Agency of Medicines and Medical Devices (AEMPS; PEI18-140) to produce clinical-grade scaffolds from healthy pericardium of cadaveric donors, and currently being used in a clinical trial [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Local administration of porcine immunomodulatory, chemotactic and angiogenic extracellular vesicles using engineered cardiac scaffolds for myocardial infarction

Monguió‐Tortajada

Prat‐Vidal

Morón-Font

et al. 2021

Bioactive Materials

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The administration of extracellular vesicles (EV) from mesenchymal stromal cells (MSC) is a promising cell-free nanotherapy for tissue repair after myocardial infarction (MI). However, the optimal EV delivery strategy remains undetermined. Here, we designed a novel MSC-EV delivery, using 3D scaffolds engineered from decellularised cardiac tissue as a cell-free product for cardiac repair. EV from porcine cardiac adipose tissue-derived MSC (cATMSC) were purified by size exclusion chromatography (SEC), functionally analysed and loaded to scaffolds. cATMSC-EV markedly reduced polyclonal proliferation and pro-inflammatory cytokines production (IFNγ, TNFα, IL12p40) of allogeneic PBMC. Moreover, cATMSC-EV recruited outgrowth endothelial cells (OEC) and allogeneic MSC, and promoted angiogenesis. Fluorescently labelled cATMSC-EV were mixed with peptide hydrogel, and were successfully retained in decellularised scaffolds. Then, cATMSC-EV-embedded pericardial scaffolds were administered in vivo over the ischemic myocardium in a pig model of MI. Six days from implantation, the engineered scaffold efficiently integrated into the post-infarcted myocardium. cATMSC-EV were detected within the construct and MI core, and promoted an increase in vascular density and reduction in macrophage and T cell infiltration within the damaged myocardium. The confined administration of multifunctional MSC-EV within an engineered pericardial scaffold ensures local EV dosage and release, and generates a vascularised bioactive niche for cell recruitment, engraftment and modulation of short-term post-ischemic inflammation.

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Section: Discussionmentioning

confidence: 99%

Local administration of porcine immunomodulatory, chemotactic and angiogenic extracellular vesicles using engineered cardiac scaffolds for myocardial infarction

Monguió‐Tortajada

Prat‐Vidal

Morón-Font

et al. 2021

Bioactive Materials

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“…Finally, we were able to demonstrate that hPL preparations display a unique profile of factors that are actively taken up by WJ-MSC to support efficient cell expansion while preserving their biological and potential therapeutic features. Advanced Therapy Medicinal Products (ATMP) based on WJ-MSC are currently being under intense development as cell therapeutics due to their regenerative characteristics, potent immunomodulatory properties, low risk for carrying somatic mutations, demonstrated effectivity and absence of adverse effects in the clinical setting, making them a promising therapeutic resource for the treatment of several pathologies involving regeneration of tissue injuries in several systems (neural, myocardial, skin, liver, kidney, cartilage, bone, muscle) [ 18 , 19 ]. Production of MSC-based cellular therapies for clinical use requires the standardization of critical methods for isolation, expansion and conservation of WJ-MSC under conditions that comply with standards of good manufacturing practices (GMP), hereby ensuring proper identity, purity, viability, stability and quantity parameters of the cell compound present in the final product.…”

Section: Discussionmentioning

confidence: 99%

Human Platelet Lysate Supports Efficient Expansion and Stability of Wharton’s Jelly Mesenchymal Stromal Cells via Active Uptake and Release of Soluble Regenerative Factors

Cañas-Arboleda¹,

Beltrán²,

Medina³

et al. 2020

IJMS

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Manufacturing of mesenchymal stromal cell (MSC)-based therapies for regenerative medicine requires the use of suitable supply of growth factors that enhance proliferation, cell stability and potency during cell expansion. Human blood derivatives such as human platelet lysate (hPL) have emerged as a feasible alternative for cell growth supplement. Nevertheless, composition and functional characterization of hPL in the context of cell manufacturing is still under investigation, particularly regarding the content and function of pro-survival and pro-regenerative factors. We performed comparative analyses of hPL, human serum (hS) and fetal bovine serum (FBS) stability and potency to support Wharton’s jelly (WJ) MSC production. We demonstrated that hPL displayed low inter-batch variation and unique secretome profile that was not present in hS and FBS. Importantly, hPL-derived factors including PDGF family, EGF, TGF-alpha, angiogenin and RANTES were actively taken up by WJ-MSC to support efficient expansion. Moreover, hPL but not hS or FBS induced secretion of osteoprotegerin, HGF, IL-6 and GRO-alpha by WJ-MSC during the expansion phase. Thus, hPL is a suitable source of factors supporting viability, stability and potency of WJ-MSC and therefore constitutes an essential raw material that in combination with WJ-MSC introduces a great opportunity for the generation of potent regenerative medicine products.

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“…[ 231 ] Recently, the first in‐human cardiac bioimplant, named PeriCord , was implanted as an advanced‐therapy medicinal product in injured myocardium clinical trials. [ 232 ] The bioimplant incorporates Wharton's jelly‐MSCs from the umbilical cord as the active ingredient and human decellularized, lyophilized, and sterilized pericardium as the supporting cell material (vehicle) for surgical implantation. Decellularized tissues or organs contain natural hierarchical nano, micro, and macrostructures of endogenous tissues that do not require further biofunctionalization.…”

Section: Implementation Of Hierarchical Tissue Constructsmentioning

confidence: 99%

Recent Advances in Regenerative Tissue Fabrication: Tools, Materials, and Microenvironment in Hierarchical Aspects

Ratri

Brilian

Setiawati

et al. 2021

Advanced NanoBiomed Research

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As part of regenerative medicine, artificial, hierarchical tissue engineering is a favorable approach to satisfy the needs of patients for new tissues and organs to replace those with defects caused by age, disease, or trauma or to correct congenital disabilities. However, the application of tissue engineering faces critical issues, such as the biocompatibility of the fabricated tissues and organs, the scaffolding, the complex biomechanical processes within cells, and the regulation of cell biology. Although fabrication strategies, including the traditional bioprinting, photolithography, and organ‐on‐a‐chip methods, as well as combinations of fabrication processes, face many challenges, they are methods that can be used in hierarchical tissue engineering. The strategic approach to synthetic, hierarchical tissue engineering is to use a combination of several technologies incorporating material science, cell biology, additive manufacturing (AM), on‐a‐chip strategies, and biomechanics. Herein, in a review, the current materials and biofabrication strategies of various artificial hierarchical tissues are discussed based on the level of tissue complexity from nano to macrosize and the adaptive interactions between cells and the scaffolding surrounding the incorporated cells.

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First-in-human PeriCord cardiac bioimplant: Scalability and GMP manufacturing of an allogeneic engineered tissue graft

Cited by 33 publications

References 35 publications

Local administration of porcine immunomodulatory, chemotactic and angiogenic extracellular vesicles using engineered cardiac scaffolds for myocardial infarction

Local administration of porcine immunomodulatory, chemotactic and angiogenic extracellular vesicles using engineered cardiac scaffolds for myocardial infarction

Human Platelet Lysate Supports Efficient Expansion and Stability of Wharton’s Jelly Mesenchymal Stromal Cells via Active Uptake and Release of Soluble Regenerative Factors

Recent Advances in Regenerative Tissue Fabrication: Tools, Materials, and Microenvironment in Hierarchical Aspects

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