Dataset Information

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

ABSTRACT:

Background

Small cardiac tissue engineering constructs show promise for limiting post-infarct sequelae in animal models. This study sought to scale-up a 2-cm² preclinical construct into a human-size advanced therapy medicinal product (ATMP; PeriCord), and to test it in a first-in-human implantation.

Methods

The PeriCord is a clinical-size (12-16 cm²) decellularised pericardial matrix colonised with human viable Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs). WJ-MSCs expanded following good manufacturing practices (GMP) met safety and quality standards regarding the number of cumulative population doublings, genomic stability, and sterility. Human decellularised pericardial scaffolds were tested for DNA content, matrix stiffness, pore size, and absence of microbiological growth.

Findings

PeriCord implantation was surgically performed on a large non-revascularisable scar in the inferior wall of a 63-year-old male patient. Coronary artery bypass grafting was concomitantly performed in the non-infarcted area. At implantation, the 16-cm² pericardial scaffold contained 12·5 × 10⁶ viable WJ-MSCs (85·4% cell viability; <0·51 endotoxin units (EU)/mL). Intraoperative PeriCord delivery was expeditious, and secured with surgical glue. The post-operative course showed non-adverse reaction to the PeriCord, without requiring host immunosuppression. The three-month clinical follow-up was uneventful, and three-month cardiac magnetic resonance imaging showed ~9% reduction in scar mass in the treated area.

Interpretation

This preliminary report describes the development of a scalable clinical-size allogeneic PeriCord cardiac bioimplant, and its first-in-human implantation.

Funding

La Marató de TV3 Foundation, Government of Catalonia, Catalan Society of Cardiology, "La Caixa" Banking Foundation, Spanish Ministry of Science, Innovation and Universities, Institute of Health Carlos III, and the European Regional Development Fund.

SUBMITTER: Prat-Vidal C

PROVIDER: S-EPMC7163319 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Prat-Vidal Cristina C Rodríguez-Gómez Luciano L Aylagas Miriam M Nieto-Nicolau Nuria N Gastelurrutia Paloma P Agustí Elba E Gálvez-Montón Carolina C Jorba Ignasi I Teis Albert A Monguió-Tortajada Marta M Roura Santiago S Vives Joaquim J Torrents-Zapata Silvia S Coca María Isabel MI Reales Laura L Cámara-Rosell María Luisa ML Cediel Germán G Coll Ruth R Farré Ramon R Navajas Daniel D Vilarrodona Anna A García-López Joan J Muñoz-Guijosa Christian C Querol Sergi S Bayes-Genis Antoni A

EBioMedicine 20200415

<h4>Background</h4>Small cardiac tissue engineering constructs show promise for limiting post-infarct sequelae in animal models. This study sought to scale-up a 2-cm<sup>2</sup> preclinical construct into a human-size advanced therapy medicinal product (ATMP; PeriCord), and to test it in a first-in-human implantation.<h4>Methods</h4>The PeriCord is a clinical-size (12-16 cm<sup>2</sup>) decellularised pericardial matrix colonised with human viable Wharton's jelly-derived mesenchymal stromal cell ...[more]

PMID: 32304998

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Project description:BackgroundHematopoietic stem cell transplantation (HSCT) is an approach that has significantly improved the prognosis and survival of hematological patients. However, ovarian dysfunction and infertility following HSCT have gained increasing attention. Live births have been reported following ovarian tissue cryopreservation prior to HSCT and subsequent retransplantation of these tissues. Still, the feasibility of ovarian tissue cryopreservation (OTC) following graft failure (GF) of HSCT remains unknown. In this study, we report the first case of OTC following a GF of allogenic HSCT (allo-HSCT), as well as the cryopreservation of four MII oocytes via in vitro maturation with informed consent. Despite the lack of clinical outcomes after cryopreserved ovarian tissue retransplantation, we documented an interesting case in a woman after GF of allo-HSCT exhibiting functional ovaries and emphasized a clinical dilemma: whether OTC should be offered to women suffering from GF of HSCT.Case presentationA 22-year-old woman with severe aplastic anemia who had suffered GF of allo-HSCT from her sibling brother [HLA allele match (7/10)] with a reduced dose conditioning regimen including fludarabine, cyclophosphamide, and antithymocyte globulin came to our reproductive center for fertility preservation, as she was about to receive the second allo-HSCT. We evaluated the ovarian reserve of this patient. Hormone assessments showed an anti-Müllerian hormone level of 3.921 ng/mL, a follicle-stimulating hormone level of 5.88 IU/L, a luteinizing hormone level of 10.79 IU/L, and an estradiol level of 33.34 pg/mL. Antral follicle counts accessed transvaginally showed 12-15 follicles. All assessments indicated a well-protected ovarian reserve. Due to the urgency of the second allo-HSCT, the patient decided to undergo ovarian cryopreservation. Laparoscopic surgery proceeded. Ovarian tissues were successfully cryopreserved using vitrification technology, and histologic evaluation demonstrated a follicle density of 20 per 2 × 2 mm2 biopsy with good viability. Four MII oocytes were obtained via in vitro maturation technology and cryopreserved. After the second HSCT, the patient relieved from aplastic anemia but suffered iatrogenic premature ovarian failure as predicted.ConclusionOTC is applicable to fertility preservation in those undergoing GF of HSCT with benign hematological disorders and especially those who are about to receive the second HSCT.

Dataset Information

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

Background

Methods

Findings

Interpretation

Funding

Publications

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

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