Extramedullary Hematopoiesis (EMH) in Laboratory Animals: Offering an Insight into Stem Cell Research

Abstract

Extramedullary hematopoiesis (EMH) is a pathological process secondary to underlying bone marrow (BM) insufficiency in adults. It is characterized by the emergence of multipotent hematopoietic progenitors scattered around the affected tissue, most likely in the spleen, liver, and lymph node, etc. EMH in patients frequently receives less medical attention and is neglected unless a compressive or obstructive hematopoietic mass appears to endanger the patient's life. However, on a biological basis, EMH reflects the alteration of relationships among hematopoietic stem and progenitor cells (HSPCs) and their original and new microenvironments. The ability of hematopoietic stem cells (HSCs) to mobilize from the bone marrow and to accommodate and function in extramedullary tissues is rather complicated and far from our current understanding. Fortunately, many reports from the studies of drugs and genetics using animals have incidentally found EMH to be involved. Thereby, the molecular basis of EMH could further be elucidated from those animals after cross-comparison. A deeper understanding of the extramedullary hematopoietic niche could help expand stem cells in vitro and establish a better treatment in patients for stem cell transplantation.

Toxicological characterisation of two novel selective aryl hydrocarbon receptor modulators in Sprague-Dawley rats

“…However, a multitude of factors (including xenobiotics) which cause e.g. local hypoxia, bone marrow failure or myelotoxicity can elicit it in laboratory animals, most frequently in spleen but also in liver (Chiu, et al 2015). In the present case, it is tempting to link it with the auricular hyperaemia, because both could represent a response to tissue hypoxia.…”

Myeloid Cells Restrict MCMV and Drive Stress-Induced Extramedullary Hematopoiesis through STAT1

“…The spleen functions as a site for EMH, particularly under stress conditions (Chiu et al, 2015; Kim, 2010). Splenomegaly and spleen rupture caused by excessive EMH is a complication of CMV infection in humans (Alliot et al, 2001; Duarte et al, 2003).…”

“…As bone marrow failure frequently occurs during CMV infection after transplantation and is associated with pancytopenia and a poor prognosis, our findings are of clear clinical significance (Almeida-Porada and Ascensăo, 1996; Lin et al, 2011; Mutter et al, 1988; Sato et al, 2011; Sing and Ruscetti, 1995). EMH is a compensatory response to hematopoietic stress in humans and mice and is frequently induced by microbial infections (Chiu et al, 2015). During CMV infection, EMH causes splenomegaly, with splenic rupture being a rare but fatal complication (Alliot et al, 2001; Duarte et al, 2003).…”

Presence of SCF/CXCL12 double‐positive large blast‐like cells at the site of cutaneous extramedullary haematopoiesis

“…2 Genetic depletion of SCF in the SCF + /CXCL12 + MSC-derived cells impairs the haematopoietic function of the bone marrow in mice. 5 Herein, we report a case of cutaneous EMH where SCF + /CXCL12 + cells were sought for immunohistochemically. 4 These suggest the presence of a heterogeneity of SCF + /CXCL12 + cells with different functions in different sites.…”

“…Furthermore, little is known about EMH in human skin. 5 Herein, we report a case of cutaneous EMH where SCF + /CXCL12 + cells were sought for immunohistochemically.…”