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

The role of bone marrow niche in stem cell aging, diseases and cancer

I wrote a lot about the stem cell niche [1], precisely about hematopoietic niche in bone marrow. I love this topic. The niche is an object of intensive investigation right now, because it plays an important role not only in stem cell maintenance, but also in aging and some diseases. However, many aspects of bone marrow niche study remain controversial [2].

I’d like to summarize a little the recent progress in understanding of the hematopoietic niche.

normal niche and stem cell quiescence
There is a common assumption, based upon experimental data, that a normal niche is required for maintain normal function of adult stem cells, hematopoietic (HSC) for instance, including one of the most important qualities – quiescence. Turns out that in embryonic development, the HSC niche doesn’t play so big a role as in adult, because needs of the growing embryo. In postnatal period of life hematopoietic system needs some “insurance” or protection in case of disasters (injuries). That’s where bone marrow niche comes up as an ideal place to keep HSC dormant or quiescent. Ideal, but not the only one. Splenic HSC [3] and even adipose-derived HSC [4] can also save lethally irradiated mice. But quiescence of splenic HSC is much inferior [3] compared to bone marrow counterparts.

However, niche-HSC-quiescence relationships are not “completely mutual”. HSC spontaneously leaves the niches daily and egress in circulation [5] without entering into cell cycle. So, it turns out that specific type of niche is not absolutely required to keep HSC quiescent. HSC can stay in G-0 phase of cell cycle in circulation (blood or lymph) and in different tissue-specific niches (spleen, bone marrow).

aged niche
It was shown before that aging phenomena of HSC [6] explained mostly their intrinsic qualities [7]. Now it turns out that it also, at least in part, could be explained by aged bone marrow niche (extrinsic mechanism). Very nice paper came up recently from Amy Wagers group at Harvard Stem Cell Institute, which showed that the aged niche is what really matters in aging of HSC [8]. At least one component of the niche – osteoblasts increased in number with age in similar manner to HSC. The authors showed that old bone marrow niche can be rejuvenated by magic circulating factors [8] in young blood.

niche-based diseases
Currently there is mounting evidence that niche abnormalities can be very important in hematological diseases development. For example, myeloproliferative disorders [9] (MPD), myelofibrosis [10], myeloma [11] and myelodysplastic syndrome. More evidences should come this year. The question also should be addressed whether transfer of abnormal niche is capable of transfering disease.

niche and cancer
There is no doubt right now that the bone marrow niche is largely involved in development of hematological malignancies [12] and solid metastatic tumors [13]. Cancer cells can migrate in bone marrow and hijack a niche [14], modifying it in order to serve disease progression [15]. In leukemia, we can see another way of niche involvement in disease development. For example, human mesenchymal stromal progenitor cells, derived from acute myelogenous [14] and acute lymphoblastic [16] leukemic bone marrow samples, have clonal genetic abnormalities.

This scheme that I drew represents a simplistic view of hematopoietic bone marrow niche interaction and significance.

niche

(adapted from David Scadden (2010), modified. Dotted lines represent possible transition from one state to another that needs to be validated in future research.)