Impact of COVID-19 and Future Emerging Viruses on Hematopoietic Cell Transplantation and Other Cellular Therapies

COVID-19, where Co stands for corona, VI stands for virus, and D denotes disease, in the recent past referred to as 2019 novel coronavirus or 2019-nCoV, has impacted numerous lives and businesses, and has led to a surreal emergency state within world communities. COVID-19 and the future emergence of dangerous viruses will have strong and as yet possibly unanticipated consequences and impact on the present and future use of cellular therapies. In this commentary, we offer a dispassionate assessment of where we believe COVID-19, as well as future emerging viruses, might compromise successful cell transplantation (Fig. 1). These therapies include hematopoietic cell transplantation (HCT) using umbilical cord blood (CB), bone marrow (BM), and mobilized peripheral blood, which contain hematopoietic stem (HSC) and progenitor (HPC) cells, as well as various cellular populations involved in the emerging fields of reparative and regenerative medicine. Such cell populations include HSC, HPC, mesenchymal stem/stromal cells (MSC), and immune cells such as lymphocytes used in chimeric antigen receptor (CAR) T-cell therapies, as well as pluripotent stem cell–based therapies

Hypoxia Signaling Pathway in Stem Cell Regulation: Good and Evil

Purpose of Review: This review summarizes the role of hypoxia and hypoxia-inducible factors (HIFs) in the regulation of stem cell biology, specifically focusing on maintenance, differentiation, and stress responses in the context of several stem cell systems. Stem cells for different lineages/tissues reside in distinct niches, and are exposed to diverse oxygen concentrations. Recent studies have revealed the importance of the hypoxia signaling pathway for stem cell functions. Recent Findings: Hypoxia and HIFs contribute to maintenance of embryonic stem cells, generation of induced pluripotent stem cells, functionality of hematopoietic stem cells, and survival of leukemia stem cells. Harvest and collection of mouse bone marrow and human cord blood cells in ambient air results in fewer hematopoietic stem cells recovered due to the phenomenon of Extra PHysiologic Oxygen Shock/Stress (EPHOSS). Summary: Oxygen is an important factor in the stem cell microenvironment. Hypoxia signaling and HIFs play important roles in modeling cellular metabolism in both stem cells and niches to regulate stem cell biology, and represent an additional dimension that allows stem cells to maintain an undifferentiated status and multilineage differentiation potential

Enhancing the efficacy of engraftment of cord blood for hematopoietic cell transplantation

Clinical cord blood (CB) hematopoietic cell transplantation (HCT) has progressed well since the initial successful CB HCT that saved the life of a young boy with Fanconi anemia. The recipient is alive and well now 28 years out since that first transplant with CB cells from his HLA-matched sister. CB HCT has now been used to treat over 35,000 patients with various malignant and non-malignant disorders mainly using HLA-matched or partially HLA-disparate allogeneic CB cells. There are advantages and disadvantages to using CB for HCT compared to other sources of transplantable hematopoietic stem (HSC) and progenitor (HPC) cells. One disadvantage of the use of CB as a source of transplantable HSC and HPC is the limited number of these cells in a single CB collected, and slower time to neutrophil, platelet and immune cell recovery. This review describes current attempts to: increase the collection of HSC/HPC from CB, enhance the homing of the infused cells, ex-vivo expand numbers of collected HSC/HPC and increase production of the infused CB cells that reach the marrow. The ultimate goal is to manipulate efficiency and efficacy for safe and economical use of single unit CB HCT

Inhibiting HDAC for human hematopoietic stem cell expansion

In this issue of the JCI, Chaurasia and colleagues report an impressive ex vivo expansion of HSCs from human cord blood (CB) using cytokines and altering epigenetic modifications. The application of this protocol provides information that has potential for clinical consideration. The enhanced expansion of CB HSCs is a substantial advance over recent work from the Chaurasia and Hoffman group, in which ex vivo production of human erythroid progenitor cells from CB was promoted by chromatin modification. Moreover, this study takes advantage of information from the rapidly emerging, but not yet fully elucidated, field of epigenetics

RHEX in the mix of erythropoietin signaling molecules

Comment on RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development. [J Exp Med. 201

Mechanism Unknown: Prostaglandin E2 May Improve HSC Therapies

A recent publication in Nature by North et al. (2007) has implicated the eicosanoid prostaglandin E2 in enhancement of hematopoietic stem cell function in zebrafish and in mice. This work may have practical therapeutic value, but much remains to be determined before this possibility is realized

Erythropoietin Surprises: An Immune Saga

Erythropoietin (EPO) an erythropoietic stimulating agent also exerts effects on other cell systems. Nairz et al. (2011) now link EPO and intracellular signaling through the EPO receptor (EPOR) to innate immune cell activity via macrophages

The Economics of “Wireless Net Neutrality”

None.

Addressing the Next Wave of Internet Regulation: The Case For Equal Opportunity

In October 2009, the Federal Communications Commission released a Notice of Proposed Rule Making in which it asked for guidance on how to convert a principle of “nondiscrimination on the Internet” into a practical rule for broadband service providers. The ultimate formulation of the nondiscrimination principle could have a significant economic effect on economic welfare in the short term and on innovation. In this paper, we explain the economics of discrimination and offer a new approach for identifying anticompetitive discrimination. Discrimination raises concerns when it interferes with what is often referred to as “equality of opportunity.” However, the Commission’s proposed nondiscrimination policy, which would limit the ability of service providers and content providers to contract on terms that (1) are mutually agreeable to both parties, (2) are available to all prospective consumers, and (3) do not impose significantly externalities on third parties, is inimical to promoting equality of opportunity. Moreover, given the twosided nature of the Internet access market, a blanket rule forbidding broadband service providers from offering quality of service to content providers (and charging for it) would likely harm endusers and certain content providers.