Extramedullary hematopoiesis: Elucidating the function of the hematopoietic stem cell niche (Review)

Yamamoto,Kouhei; Miwa,Yukako; Abe‑Suzuki,Shiho; Abe,Shinya; Kirimura,Susumu; Onishi,Iichiroh; Kitagawa,Masanobu; Kurata,Morito

doi:10.3892/mmr.2015.4621

Extramedullary hematopoiesis: Elucidating the function of the hematopoietic stem cell niche (Review)

Authors:
- Kouhei Yamamoto
- Yukako Miwa
- Shiho Abe‑Suzuki
- Shinya Abe
- Susumu Kirimura
- Iichiroh Onishi
- Masanobu Kitagawa
- Morito Kurata
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Affiliations: Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo‑ku, Tokyo 113‑8519, Japan, Department of Pathology, Kanazawa Medical University Hospital, Kanazawa, Ishikawa 920‑0293, Japan
Published online on: November 27, 2015 https://doi.org/10.3892/mmr.2015.4621
Pages: 587-591

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Abstract

Extramedullary hematopoiesis (EMH) occurs under various circumstances, including during embryonic/developmental periods, pathological status secondary to insufficient bone marrow function or ineffective hematopoiesis, in hematological disorders, for example malignancies, as well as stromal disorders of the bone. EMH is characterized by hematopoietic cell accumulations in multiple body locations. Common EMH locations observed in clinical and pathological practice include the spleen, liver, lymph nodes and para‑vertebral regions. Among the various organs associated with EMH, the spleen offers a unique site for evaluation of hematopoietic stem cell (HSC)/niche interactions, as this organ is one of the most common sites of EMH. However, the spleen does not have a major role in embryonic/developmental hematopoiesis. A recent study by our group revealed that circulating HSCs may be trapped by chemokine (C‑X‑C motif) ligand 12 (CXCL12)‑positive cells at the margin of sinuses near CXCL12‑positive endothelial cells, resulting in the initiation of the first step of EMH, which is a similar mechanism to bone marrow hematopoiesis. The present review briefly discusses the environment of EMH in extramedullary spaces in order to investigate the mechanisms underlying HSC maintenance, and aid the elucidation of the niche‑stem cell interactions that occur in the bone marrow.

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1	Sohawon D, Lau KK, Lau T and Bowden DK: Extra medullary haematopoiesis: a pictorial review of its typical and atypical locations. J Med Imaging Radiat Oncol. 56:534–538. 2012. View Article : Google Scholar
2	Tsamandas AC, Jain AB, Raikow RB, Demetris AJ, Nalesnik MA and Randhawa PS: Extramedullary hematopoiesis in the allograft liver. Mod Pathol. 8:671–674. 1995.PubMed/NCBI
3	Vassiliou V, Papamichael D, Lutz S, Eracleous E, Kountourakis P, Polyviou P, Michaelides I, Shoukris M and Andreopoulos D: Presacral extramedullary hematopoiesis in a patient with eectal adenocarcinoma: report of a case and literature review. J Gastrointest Cancer Feb. 10:2012.Epub ahead of print.
4	Macki M, Bydon M, Papademetriou K, Gokaslan Z and Bydon A: Presacral extramedullary hematopoiesis: an alternative hypothesis. J Clin Neurosci. 20:1664–1668. 2013. View Article : Google Scholar : PubMed/NCBI
5	Johns JL and Christopher MM: Extramedullary hematopoiesis: a new look at the underlying stem cell niche, theories of development and occurrence in animals. Vet Pathol. 49:508–523. 2012. View Article : Google Scholar : PubMed/NCBI
6	Mendelson A and Frenette PS: Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat Med. 20:833–846. 2014. View Article : Google Scholar : PubMed/NCBI
7	Flores-Figueroa E, Varma S, Montgomery K, et al: Distinctive contact between CD34+hematopoietic progenitors and CXCL12+CD271+mesenchymal stromal cells in benign and myelodysplastic bone marrow. Lab Invest. 92:1330–1341. 2012. View Article : Google Scholar : PubMed/NCBI
8	Lilly AJ, Johnson WE and Bunce CM: The haematopoietic stem cell niche: new insights into the mechanisms regulating haematopoietic stem cell behaviour. Stem Cells Int. 274564:2011.
9	Lo Celso C, Fleming HE, Wu JW, et al: Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature. 457:92–96. 2009. View Article : Google Scholar
10	Kiel MJ and Morrison SJ: Uncertainty in the niches that maintain haematopoietic stem cells. Nat Rev Immunol. 8:290–301. 2008. View Article : Google Scholar : PubMed/NCBI
11	Ding L, Saunders TL, Enikolopov G and Morrison SJ: Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 481:457–462. 2012. View Article : Google Scholar : PubMed/NCBI
12	Levesque JP and Winkler IG: Hierarchy of immature hematopoietic cells related to blood flow and niche. Curr Opin Hematol. 18:220–225. 2011. View Article : Google Scholar : PubMed/NCBI
13	Nagasawa T, Omatsu Y and Sugiyama T: Control of hematopoietic stem cells by the bone marrow stromal niche: the role of reticular cells. Trends Immunol. 32:315–320. 2011. View Article : Google Scholar : PubMed/NCBI
14	Mendez-Ferrer S, Michurina TV, Ferraro F, et al: Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 466:829–834. 2010. View Article : Google Scholar : PubMed/NCBI
15	Yamazaki S, Ema H, Karlsson G, et al: Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche. Cell. 147:1146–1158. 2011. View Article : Google Scholar : PubMed/NCBI
16	Avecilla ST, Hattori K, Heissig B, et al: Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. 10:64–71. 2004. View Article : Google Scholar : PubMed/NCBI
17	Ara T, Tokoyoda K, Sugiyama T, et al: Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity. 19:257–267. 2003. View Article : Google Scholar : PubMed/NCBI
18	Ellyard JI, Avery DT, Mackay CR, et al: Contribution of stromal cells to the migration, function and retention of plasma cells in human spleen: potential roles of CXCL12, IL-6 and CD54. Eur J Immunol. 35:699–708. 2005. View Article : Google Scholar : PubMed/NCBI
19	Miwa Y, Hayashi T, Suzuki S, Abe S, Onishi I, Kirimura S, Kitagawa M and Kurata M: Up-regulated expression of CXCL12 in human spleens with extramedullary haematopoiesis. Pathology. 45:408–416. 2013. View Article : Google Scholar : PubMed/NCBI
20	Visnjic D, Kalajzic Z, Rowe DW, et al: Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 103:3258–3264. 2004. View Article : Google Scholar : PubMed/NCBI
21	Wolf BC and Neiman RS: Hypothesis: splenic filtration and the pathogenesis of extramedullary hematopoiesis in agnogenic myeloid metaplasia. Hematol Pathol. 1:77–80. 1987.PubMed/NCBI
22	MacSween RMN, Burt AD, Portmann BC, et al: Pathology of the Liver, 4th ed. Diagn Cytopathol. 29:432003. View Article : Google Scholar
23	Schlitt HJ, Schäfers S, Deiwick A, Eckardt KU, Pietsch T, Ebell W, Nashan B, Ringe B, Wonigeit K and Pichlmayr R: Extramedullary erythropoiesis in human liver grafts. Hepatology. 21:689–696. 1995. View Article : Google Scholar : PubMed/NCBI
24	Tsamandas AC, Jain AB, Raikow RB, Demetris AJ, Nalesnik MA and Randhawa PS: Extramedullary hematopoiesis in the allograft liver. Mod Pathol. 8:671–674. 1995.PubMed/NCBI
25	Craig CE, Quaglia A and Dhillon AP: Extramedullary haematopoiesis in massive hepatic necrosis. Histopathology. 45:518–525. 2004. View Article : Google Scholar : PubMed/NCBI
26	Sohawon D, Lau KK, Lau T and Bowden DK: Extra-medullary haematopoiesis: a pictorial review of its typical and atypical locations. J Med Imaging Radiat Oncol. 56:538–534. 2012. View Article : Google Scholar : PubMed/NCBI
27	O'Malley DP: Benign extramedullary myeloid proliferations. Mod Pathol. 20:405–415. 2007. View Article : Google Scholar : PubMed/NCBI
28	Tavian M, Biasch K, Sinka L, Vallet J and Péault B: Embryonic origin of human hematopoiesis. Int J Dev Biol. 54:1061–1065. 2010. View Article : Google Scholar : PubMed/NCBI
29	Tavian M, Cortés F, Charbord P, Labastie MC and Péault B: Emergence of the haematopoietic system in the human embryo and foetus. Haematologica. 84(Suppl EHA-4): 1–3. 1999.
30	Georgiades CS, Neyman EG, Francis IR, Sneider MB and Fishman EK: Typical and atypical presentations of extramedullary hemopoiesis. AJR Am J Roentgenol. 179:1239–1243. 2002. View Article : Google Scholar : PubMed/NCBI
31	Tavian M and Péault B: The changing cellular environments of hematopoiesis in human development in utero. Exp Hematol. 33:1062–1069. 2005. View Article : Google Scholar : PubMed/NCBI
32	Palatnik A, Narayan R and Walters M: Extramedullary hematopoiesis involving uterus, fallopian tubes, and ovaries, mimicking bilateral tuboovarian abscesses. Int J Gynecol Pathol. 31:584–587. 2012. View Article : Google Scholar : PubMed/NCBI
33	Akbulut S, Yavuz R, Akansu B, Sogutcu N, Arikanoglu Z and Basbug M: Ectopic bone formation and extramedullary hematopoiesis in the thyroid gland: report of a case and literature review. Int Surg. 96:260–265. 2011. View Article : Google Scholar
34	Radopoulos D, Tzakas K and Tahmatzopoulos A: A rare case of renal oncocytoma associated with erythrocytosis: case report. BMC Urol. 23:262006. View Article : Google Scholar
35	Tavian M and Péault B: Embryonic development of the human hematopoietic system. Int J Dev Biol. 49:243–250. 2005. View Article : Google Scholar : PubMed/NCBI
36	Neiman RS, Barcos M, Berard C, Bonner H, Mann R, Rydell RE and Bennett JM: Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer. 48:1426–1437. 1981. View Article : Google Scholar : PubMed/NCBI
37	Tavassoli M and Weiss L: An electron microscopic study of spleen in myelofibrosis with myeloid metaplasia. Blood. 42:267–279. 1973.PubMed/NCBI
38	Yoshida H, Kawane K, Koike M, et al: Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells. Nature. 437:754–758. 2005. View Article : Google Scholar : PubMed/NCBI
39	Chasis JA and Mohandas N: Erythroblastic islands: niches for erythropoiesis. Blood. 112:470–478. 2008. View Article : Google Scholar : PubMed/NCBI
40	Sadahira Y and Mori M: Role of the macrophage in erythropoiesis. Pathol Int. 49:841–848. 1999. View Article : Google Scholar : PubMed/NCBI
41	Sonoda Y and Sasaki K: Surface morphology of the central macrophages of erythroblastic islets in the spleen of aged and pregnant mice: an immunohistochemical light microscopic study. Arch Histol Cytol. 71:155–161. 2008. View Article : Google Scholar
42	Sonoda Y: Immunophenotype and functional characteristics of human primitive CD34-negative hematopoietic stem cells: the significance of the intra-bone marrow injection. J Autoimmun. 30:136–144. 2008. View Article : Google Scholar : PubMed/NCBI
43	De Jong MO, Wagemaker G and Wognum AW: Separation of myeloid and erythroid progenitors based on expression of CD34 and c-kit. Blood. 86:4076–4085. 1995.PubMed/NCBI
44	Cesta MF: Normal structure, function and histology of the spleen. Toxicol Pathol. 34:455–465. 2006. View Article : Google Scholar
45	Mebius RE and Kraal G: Structure and function of the spleen. Nat Rev Immunol. 5:606–616. 2005. View Article : Google Scholar : PubMed/NCBI
46	Mueller SN and Ahmed R: Lymphoid stroma in the initiation and control of immune responses. Immunol Rev. 224:284–294. 2008. View Article : Google Scholar : PubMed/NCBI
47	Asakura A and Rudnicki MA: Side population cells from diverse adult tissues are capable of in vitro hematopoietic differentiation. Exp Hematol. 30:1339–1345. 2002. View Article : Google Scholar : PubMed/NCBI
48	Saito H, Yokoi Y, Watanabe S, et al: Reticular meshwork of the spleen in rats studied by electron microscopy. Am J Anat. 181:235–252. 1988. View Article : Google Scholar : PubMed/NCBI
49	Wright DE, Wagers AJ, Gulati AP, et al: Physiological migration of hematopoietic stem and progenitor cells. Science. 294:1933–1936. 2001. View Article : Google Scholar : PubMed/NCBI
50	Stroncek D, Shawker T, Follmann D and Leitman SF: G-CSF-induced spleen size changes in peripheral blood progenitor cell donors. Transfusion. 43:609–613. 2003. View Article : Google Scholar : PubMed/NCBI
51	Picardi M, De Rosa G, Selleri C, Scarpato N, Soscia E, Martinelli V, Ciancia R and Rotoli B: Spleen enlargement following recombinant human granulocyte colony-stimulating factor administration for peripheral blood stem cell mobilization. Haematologica. 88:794–800. 2003.PubMed/NCBI
52	O'Neill HC, Griffiths KL, Periasamy P, et al: Spleen as a site for hematopoiesis of a distinct antigen presenting cell type. Stem Cells Int. 954275:2011.
53	Sivasubramaniyan K, Lehnen D, Ghazanfari R, Sobiesiak M, Harichandan A, Mortha E, Petkova N, Grimm S, Cerabona F, de Zwart P, et al: Phenotypic and functional heterogeneity of human bone marrow- and amnion-derived MSC subsets. Ann NY Acad Sci. 1266:94–106. 2012. View Article : Google Scholar : PubMed/NCBI
54	Lucas D, Scheiermann C, Chow A, Kunisaki Y, Bruns I, Barrick C, Tessarollo L and Frenette PS: Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration. Nat Med. 19:695–703. 2013. View Article : Google Scholar : PubMed/NCBI
55	Ding L and Morrison SJ: Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature. 495:231–235. 2013. View Article : Google Scholar : PubMed/NCBI
56	Chute JP: Stem cell homing. Curr Opin Hematol. 13:399–406. 2006. View Article : Google Scholar : PubMed/NCBI
57	Jamieson CH, Barroga CF and Vainchenker WP: Miscreant myeloproliferative disorder stem cells. Leukemia. 22:2011–2019. 2008. View Article : Google Scholar : PubMed/NCBI