Alginate-Chitosan Microencapsulated Cells for Improving CD34+ Progenitor Maintenance and Expansion

Protocols for isolation, characterization, and transplantation of hematopoietic stem cells (HSCs) have been well established. However, difficulty in finding human leucocyte antigens (HLA)-matched donors and scarcity of HSCs are still the major obstacles of allogeneic transplantation. In this study, we developed a double-layered microcapsule to deliver paracrine factors from non-matched or low-matched HSCs to other cells. The umbilical cord blood-derived hematopoietic progenitor cells, identified as CD34+ cells, were entrapped in alginate polymer and further protected by chitosan coating. The microcapsules showed no toxicity for surrounding CD34+ cells. When CD34+ cells-loaded microcapsules were co-cultured with bare CD34+ cells that have been collected from unrelated donors, the microcapsules affected surrounding cells and increased the percentage of CD34+ cell population. This study is the first to report the potency of alginate-chitosan microcapsules containing non-HLA-matched cells for improving proliferation and progenitor maintenance of CD34+ cells.

More Bang for Your Buck: “Off-The-Shelf” Solutions for Cell Replacement Therapy

The immune barrier to transplantation has widely been recognized as the ultimate hurdle to the translation of stem cell-based therapies. In particular the polymorphic nature of the human leucocyte antigens (HLA) poses an imminent barrier to the successful engraftment of cells from other than autologous sources. To make stem cell therapies available to a larger pool of patients and a commercially viable option several groups have attempted to create hypoimmunogenic “universal” donor stem cells that evaded immune detection. The goal of this commentary is to give a brief overview of the current approaches taken and discuss challenges that need to be addressed to turn such cells into a viable commercial option.

Case report - pre-transplant testing and post-transplant monitoring for an HLA-immunized recipient in heart transplantation

We report the workflow of immunogenetic pre-transplant testing and post-transplant monitoring in the case of a recipient immunized to human leucocyte antigens (HLA) who was waitlisted for heart transplantation. The recipient underwent heart transplantation across preformed HLA class I Donor Specific Antibodies (DSAs) detected by solid phase Luminex screening method but not by complement dependent cytotoxicity (CDC) screening method. The CDC lymphocyte crossmatch, which was performed retrospectively, was a weak positive. Post-transplant DSA monitoring by Luminex method revealed the decrease of HLA-A1, A25 and B57 DSAs with, at the same time, an increase of HLA-B8 DSA, as well as weak transient non-DSA HLA-DP antibodies. This case presents the importance of extensive immunogenetic testing and monitoring for identifying recipients with increased immunological risk for successful heart transplantation.

Translation of Basic Research into Clinics: Killer Immunoglobulin-like Receptors Genes in Autoimmune and Infectious Diseases

Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIRs and HLA loci are highly polymorphic, and some of their combinations have been found to protect against viral infections or to predispose to autoimmune disorders. In particular, some activating KIRs profiles may be detrimental in autoimmune pathogenesis, and specific KIRs may be particularly aggressive in the clearance of different microorganisms, protecting individuals in the control of a given pathogen. So, considering that in the pathogenesis of many autoimmune disorders and infections innate immunity plays a key role, the recent development for KIRs characterization, diseases monitoring, and treatment becomes obvious. Here, we reviewed a growing body of evidence supporting the influence of KIRs variants and their interaction with ligands in the development of the main human autoimmune and viral diseases, highlighting the main applications in clinical practice.