A model for preservation of thymocyte-depleted thymus.
A S DiasNilsa Regina Damaceno-RodriguesT M GimenezP M OliveiraMaria Claudia Nogueira ZerbiniMagda Maria Sales Carneiro-SampaioVicente Odone FilhoMarcelo B JateneDewton de Moraes VasconcelosVanderson Geraldo RochaEstela NovakPublished in: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (2023)
DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196°C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3×106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.
Keyphrases
- end stage renal disease
- ejection fraction
- chronic kidney disease
- newly diagnosed
- case report
- cell therapy
- prognostic factors
- randomized controlled trial
- stem cells
- mesenchymal stem cells
- single cell
- patient reported outcomes
- copy number
- high resolution
- dna methylation
- peripheral blood
- open label
- study protocol
- double blind
- phase ii