RESUMO
Umbilical cord blood (UCB) serves as a source of hematopoietic stem and progenitor cells (HSPCs) utilized in the regeneration of hematopoietic and immune systems, forming a crucial part of the treatment for various benign and malignant hematological diseases. UCB has been utilized as an alternative HSPC source to bone marrow (BM). Although the use of UCB has extended transplantation access to many individuals, it still encounters significant challenges in selecting a histocompatible UCB unit with an adequate cell dose for a substantial proportion of adults with malignant hematological diseases. Consequently, recent research has focused on developing ex vivo expansion strategies for UCB HSPCs. Our results demonstrate that co-cultures with the investigated mesenchymal stromal cells (MSCs) enable a 10- to 15-fold increase in the cellular dose of UCB HSPCs while partially regulating the proliferation capacity when compared to HSPCs expanded with early acting cytokines. Furthermore, the secretory profile of UCB-derived MSCs closely resembles that of BM-derived MSCs. Moreover, both co-cultures exhibit alterations in cytokine secretion, which could potentially impact HSPC proliferation during the expansion process. This study underscores the fact that UCB-derived MSCs possess a remarkably similar supportive capacity to BM-derived MSCs, implying their potential use as feeder layers in the ex vivo expansion process of HSPCs.
Assuntos
Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Gravidez , Feminino , Adulto , Humanos , Antígenos CD34 , Sangue Fetal , Células-Tronco Hematopoéticas , Técnicas de Cocultura , Transplante de Células-Tronco Hematopoéticas/métodos , Proliferação de CélulasRESUMO
The HLA compatibility continues to be the main limitation when finding compatible donors, especially if an identical match is not found within the patient's family group. The creation of bone marrow registries allowed a therapeutic option by identifying 10/10 compatible unrelated donors (URD). However, the availability and frequency of haplotypes and HLA alleles are different among ethnic groups and geographical areas, increasing the difficulty of finding identical matches in international registries. In this study, the HLA-A, -B, -C, -DRB1, and -DQB1 loci of 1763 donors registered in the Colombian Bone Marrow Registry were typed by next-generation sequencing. A total of 52 HLA-A, 111 HLA-B, 41 HLA-C, 47 HLA-DRB1, and 20 HLA-DQB1 alleles were identified. The 3 most frequent alleles for each loci were A*24:02g (20,8%), A*02:01g (16,1%), A*01:01g (7.06%); B*35:43g (7.69%), B*40:02g (7.18%), B*44:03g (6.07%); C*04:01g (15.40%), C*01:02g (10.49%), C*07:02g (10.44%); DRB1*04:07g (11.03%), DRB1*07:01g (9.78%), DRB1*08:02g (6.72%); DQB1*03:02g (20.96%), DQB1*03:01g (17.78%) and DQB1*02:01g (16.05%). A total of 497 HLA-A-C-B-DRB1-DQB1 haplotypes were observed with a frequency greater than or equal to 0.05% (> 0.05%); the haplotypes with the highest frequency were A*24:02g~B*35:43g~C*01:02g~DQB1*03:02g~DRB1*04:07g (3.34%), A*29:02g~B*44:03g~C*16:01g~DQB1*02:01g~DRB1*07:01g (2.04%), and A*01:01g~B*08:01g~C*07:01g~DQB1*02:01g~DRB1*03:01g (1.83%). This data will allow the new Colombian Bone Marrow Donor Registry to assess the genetic heterogeneity of the Colombian population and serve as a tool of interest for future searches of unrelated donors in the country.