- Cell Trials - http://celltrials.info -

The role of spleen in adult hematopoiesis


There are many indications that the spleen can play an important role in hematopoiesis, but it remains largely unstudied. We known that hematopoietic stem cells (HSC) are trafficking during embryonic development through the spleen and reside withing the organ in postnatal hematopoiesis. It seems that spleen is the only organ where HSC can reside (not just circulate) besids bone marrow. But what do they do in the spleen?

The earliest evidence that spleen in adults can play a significant role in hematopoiesis comes form a series of experiments which were done more then 50 years ago – citation from StemBook [1]:

The ability of HSC/progenitor to migrate continuously to the bone marrow was demonstrated decades ago in experiments in which shielding of the spleen allowed mice to recover from a lethal dose of irradiation (Jacobson et al., 1949 [2]). These studies and others in the following decade (Barnes et al., 1956 [3]; Lorenz et al., 1951 [4]) clearly demonstrated that splenic HSCs could spontaneously “home” to and repopulate the bone marrow, and paved the way toward the clinical use of bone marrow transplantation (Thomas, 1995).

The modern studies of hematopoiesis in the spleen are focused on dissection of HSC phenotype, their genetic signature and cell cycle status in comparison with bone marrow counterparts. Hiromitsu Nakauchi and Hideo Ema’s group presented [5] some preliminary data on the last ASH 2008 [6] meeting:

HSCs reside in both BM and spleen throughout the life of a mouse. The spleen is the major site of extramedullary hematopoiesis in pathological conditions. The spleen serves as an active hematopoietic organ in lethally irradiated mice for a while after transplantation with BM cells.

The frequency of CD34–KSL cells in the spleen was significantly lower than that in the BM. These data indicate that functionally equivalent HSCs exist in the spleen but at a low frequency. Data from single cell-transplantation supported this notion. These data suggest that spleen HSCs contribute to hematopoiesis to some extent under physiological conditions.

Now, if HSC in spleen are fully functional and are not circulating, they should have their own niches, different from bone marrow ones.

Osteoblasts are considered to be one of the stem cell niche components. Because there are no osteoblasts in the spleen, niches in the spleen possibly functions differently from ones in the BM.

Furthermore, researchers are starting to characterize HSC niche in mouse adult spleen. Preliminary data from Takuo Mizukami study [7] (also presented during ASH’08 [6]) suggest that megakaryocyte like cells (MLC) withing the red pulp of spleen could be candidates for niche cells for HSC in mouse model of extramedullary hematopoiesis. MLC express signal molecules similar to those in osteoblastic lineage cells in bone marrow (N-Cadherin, b-Catenin, Spp1 and SDF-1a).

In this study, we first identified a candidate for EMH-niche cells and postulated a developmental mechanism in the spleen. Our findings provide a new functional insight into HSCs outside the bone marrow, and extend a new tool that supports ex vivo expansion of HSCs.

However, extramedullary hematopoiesis (EMH) models could be very different from physiological conditions (pathological vs normal niche). Another potential candidate for HSC splenic niche is stromal cells [8].

Recentlyl, Yuli Wang [9] was trying to investigate the potential significance of extramedullary hematopoiesis:

The study indicates that EMH occurs as a compensatory reaction to CTX-induced hematosuppression in the murine spleen, implying that conservation of the spleen may promote the recovery of cancer patients from chemotherapy-induced hematosuppression.

Further studies should investigate physiological role of splenic HSC and their origin. Identification of splenic hematopoietic niches could help us to understand better of HSC maintainance and develop new methods for their clinical-scale expansion.

*****************

picture credit: MEDICAL RF.COM / SCIENCE PHOTO LIBRARY [10]