Multimodal Tracking of Hematopoietic Stem Cells from Young and Old Mice Labeled with Magnetic-Fluorescent Nanoparticles and Their Grafting by Bioluminescence in a Bone Marrow Transplant Model

Autor(es)

Oliveira, Fernando A. ^[1] ; Nucci, Mariana P. ^{[1, 2]} ; Mamani, Javier B. ^[1] ; Alves, Arielly H. ^[1] ; Rego, Gabriel N. A. ^[1] ; Kondo, Andrea T. ^[1] ; Hamerschlak, Nelson ^[1] ; Junqueira, Mara S. ^[3] ; de Souza, Lucas E. B. ^[4] ; Gamarra, Lionel E. ^[1]

Afiliação do(s) autor(es)

^[1] Hosp Israelita Albert Einstein, BR-05652000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, LIM44 Hosp Clin, BR-05403000 Sao Paulo, SP - Brazil

^[3] Canc Inst State Sao Paulo ICESP, Ctr Translat Res Oncol, BR-01246000 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Hemoctr Ribeirao Preto, BR-14051060 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICINES; v. 9, n. 7 JUL 2021.
• Citações Web of Science: 1

Resumo

This study proposes an innovative way to evaluate the homing and tracking of hematopoietic stem cells from young and old mice labeled with SPIONNIRF-Rh conjugated with two types of fluorophores (NIRF and Rhodamine), and their grafting by bioluminescence (BLI) in a bone marrow transplant (BMT) model. In an in vitro study, we isolated bone marrow mononuclear cells (BM-MNC) from young and old mice, and analyzed the physical-chemical characteristics of SPIONNIRF-Rh, their internalization, cell viability, and the iron quantification by NIRF, ICP-MS, and MRI. The in vivo study was performed in a BMT model to evaluate the homing, tracking, and grafting of young and old BM-MNC labeled with SPIONNIRF-Rh by NIRF and BLI, as well as the hematological reconstitution for 120 days. 5FU influenced the number of cells isolated mainly in young cells. SPIONNIRF-Rh had adequate characteristics for efficient internalization into BM-MNC. The iron load quantification by NIRF, ICP-MS, and MRI was in the order of 10(4) SPIONNIRF-Rh/BM-MNC. In the in vivo study, the acute NIRF evaluation showed higher signal intensity in the spinal cord and abdominal region, and the BLI evaluation allowed follow-up (11-120 days), achieving a peak of intensity at 30 days, which remained stable around 10(8) photons/s until the end. The hematologic evaluation showed similar behavior until 30 days and the histological results confirm that iron is present in almost all tissue evaluated. Our results on BM-MNC homing and tracking in the BMT model did not show a difference in migration or grafting of cells from young or old mice, with the hemogram analysis trending to differentiation towards the myeloid lineage in mice that received cells from old animals. The cell homing by NIRF and long term cell follow-up by BLI highlighted the relevance of the multimodal nanoparticles and combined techniques for evaluation. (AU)

• Processo FAPESP: 14/50983-3 - INCT 2014: fluidos complexos
• Beneficiário: Antonio Martins Figueiredo Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/21470-3 - Ação terapêutica das células tronco mesenquimais da medula humana, marcadas com nanopartículas multimodais em ratos diabéticos submetidos a isquemia cerebral focal: estudo dos mecanismos celulares, moleculares e funcionais.
• Beneficiário: Lionel Fernel Gamarra Contreras
• Modalidade de apoio: Auxílio à Pesquisa - Regular