The hematopoiesis or blood formation is the formation of the cells of the blood from blood cell-forming stem cells . Many blood cells have a limited lifespan ( erythrocytes : approx. 30–120 days, platelets : approx. 3–10 days), which is why constant renewal is necessary. In an adult human, billions of mature blood cells are produced every day.
There are four different versions of the word that are believed to be correct and used in publications: haematopoiesis , haematopoiesis , haemopoiesis , and haemopoiesis . In German the form without internal i ( -poese ), in English the form with internal i ( -poiesis ) is more common. In English, e or ae is also written instead of ä ( American English : h e matopoiesis or British English : h ae matopoiesis ). The genitive stem hematocrit is hemodialysis preferable.
The first blood formation sites found in humans and mice are the so-called blood islands in the yolk sac . As the first mesodermal differentiation, homogeneous cell aggregates appear, which probably consist of hemangioblasts . The outer cells of these aggregates then differentiate into endothelium , inside erythrocytes arise , so that filled blood vessels are formed. These early, 'primitive' erythrocytes still contain cell nuclei , in contrast to those found later in the body. The first megakaryocytes and macrophages also develop . Blood islands are already active in the earliest stages of organogenesis , shortly after gastrulation . A little later than the first primitive erythrocyte precursors, permanent myeloerythroid precursors also develop in the yolk sac, but these must migrate to the liver in order to differentiate further. However, it is still unclear whether real hematopoietic stem cells, from which all types of blood cells can develop, also develop in the yolk sac.
Before the later hematopoietic organs thymus , spleen and bone marrow are formed, the fetal liver temporarily takes over the function of blood cell-forming organ, in which, alongside other types of blood cells, nucleated, 'mature' erythrocytes arise for the first time. In the fetal liver, hematopoietic stem cells are preserved and multiplied, they also mature there, so that later colonization of the bone marrow is possible. However, a new formation does not take place here or in the later haematopoietic organs. All of these organs must therefore be colonized by haematopoietic stem cells that have arisen elsewhere and find their way to their target organs via the blood flow.
These stem cells are first formed in the AGM region of the early embryo. The letters stand for aorta , gonads and mesonephros . In this region, which includes the dorsal aorta, the surrounding mesenchyme and the urogenital ridge , no differentiation into later blood cell stages takes place. For the AGM region it could be shown that the stem cells here are not formed from hemangioblasts, but from specialized endothelial cells ( hemogenic endothelial cells ) that line the aorta. Hematopoietic stem cells are also formed in the yolk sac. Depending on where they were formed, they seem to differ functionally, since it has only been possible to show that they can also produce lymphoid cells for those from the AGM region . It is therefore being discussed that the bone marrow, as a permanent organ of hematopoiesis, could only be colonized by stem cells from the AGM region. For the placenta , it was shown in mice that haematopoietic stem cells also develop there. Another possible place of education is the allantois .
In mice, after 11.5–12.5 days after fertilization, the hematopoietic stem cells migrate from the yolk sac, AGM region and placenta via the bloodstream to the liver. For 5–6 days, the stem cells multiply rapidly and differentiate into various progenitor cells . Only one or two days before the end of the approximately 20-day gestation period do both stem and progenitor cells migrate into the bone marrow. Shortly afterwards, the stem cells largely stop dividing and divide only very rarely. In further life there is a migration of haematopoietic stem cells through the blood vessel system, tissue and back into the bone marrow at a low level.
Like the fetal liver, the fetal spleen is at times a haematopoietic organ, in mice from the last third of gestation to a few weeks after birth. The hematopoietic stem cells hardly multiply here, but their differentiation into mature blood cells does.
In humans, hematopoiesis takes place in the mesenchyme of the yolk sac up to the 3rd embryonic month ( mesoblastic period ). From the 2nd embryonic month, blood formation in the fetus takes place in the liver ( hepatic period ), from the 4th fetal month also in the spleen and thymus ( hepatolineal period ), from the 6th fetal month in the spleen and bone marrow ( lienomyelopoietic period ), from the 6th to 7th month mainly in the bone marrow ( myelopoietic period ), except for lymphocytes .
The term 'adult', i.e. adult hematopoiesis, is misleading insofar as it takes place from birth. However, the term has been introduced to distinguish it from embryonic, i.e. prenatal hematopoiesis and is therefore used here accordingly. After birth, hematopoiesis occurs in the bone marrow (myelotic system) and in the lymphatic system . Blood cells are made from stem cells that pass from the bone marrow into the blood after they mature. Some of the stem cells are pluripotent , i. In other words, they can mature into both myeloid and lymphatic cells, whereas those that are already more differentiated are committed and can only differentiate in one or two specific directions.
The stem cells of different stages can be distinguished from one another by the presence ( + ) or absence ( - ) of different surface markers (proteins that are externally bound to the cell membrane ) by immunophenotyping . The least differentiated stem cells, the 'long-term-repopulating cells', are characterized, for example, in the mouse by the marker combination KIT + Sca-1 + CD34 - . These cells very rarely divide. In the next stage, they can differentiate into 'short term repopulating cells' (c-kit + Sca-1 + CD34 + ), which divide more frequently. These in turn give rise to 'common lymphoid precursors' (CLP, common lymphoid precursors) and 'common myeloid precursors' (CMP, common myeloid precursors).
If immature blood cell precursors pass into the blood, this is known as a nuclear shift .
Hematopoiesis in mice
With stem cell deficiency in the bone marrow and relative thrombocytopenia, stem cells migrate from the lungs into the bone marrow. These participate in the formation of various blood cell lines and completely eliminate the thrombocytopenia. 50% of thrombopoiesis occurs in the lungs through megakaryocytes that have migrated from the bone marrow.
Blood cell lines
As engraftment refers to the branch of hematopoiesis in which red blood cells, platelets, granulocytes, from pluripotent stem cells osteoclasts , macrophages and mast cells are formed. It takes place exclusively in the bone marrow. The other branch of hematopoiesis is known as lymphopoiesis . It is also found outside the bone marrow in the lymphatic organs .
A further distinction is made according to the type of blood cells formed and their cell origin :
- the erythropoiesis : formation of red blood cells
- the thrombopoiesis : formation of platelets
- the Megakaryopoiesis : formation of megakaryocytes
- the leucopoiesis : formation of leukocytes
- the Granulopoese : formation of granulocytes
- the Lymphopoese : formation of lymphocytes
- the Monopoese : formation of monocytes
The word hematopoiesis is derived from the ancient Greek αἷμα haíma "blood" (whose stem is recognizable in the genitive αἷματος haímatos ; hence the word formation hemat- ) and ποίησις poíēsis " doing ", "activity that produces something". Hematopoiesis literally means blood formation . The first component of Myelopoese can be traced back to μυελός myelós "marrow".
- Ludwig Heilmeyer , Herbert Begemann: blood and blood diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid. 1961, pp. 376–449, here: pp. 388–392 ( blood formation and death ).
- ^ A b D. J. Laird, UH von Andrian, AJ Wagers: Stem cell trafficking in tissue development, growth, and disease . In: Cell . tape 132 , no. 4 , February 2008, p. 612-630 , doi : 10.1016 / j.cell.2008.01.041 , PMID 18295579 .
- ↑ a b c d A. Cumano, I. Godin: Ontogeny of the hematopoietic system . In: Annual review of immunology . tape 25 , 2007, p. 745-785 , doi : 10.1146 / annurev.immunol.25.022106.141538 , PMID 17201678 .
- ↑ a b H. K. Mikkola, SH Orkin: The journey of developing hematopoietic stem cells . In: Development (Cambridge, England) . tape 133 , no. October 19 , 2006, p. 3733-3744 , doi : 10.1242 / dev.02568 , PMID 16968814 .
- ^ MF de Bruijn, X. Ma, C. Robin, K. Ottersbach, MJ Sanchez, E. Dzierzak: Hematopoietic stem cells localize to the endothelial cell layer in the midgestation mouse aorta . In: Immunity . tape 16 , no. 5 , May 2002, pp. 673-683 , PMID 12049719 ( elsevier.com ).
- ↑ KE Rhodes, C. Gekas, Y. Wang et al: The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation . In: Cell stem cell . tape 2 , no. 3 , March 2008, p. 252-263 , doi : 10.1016 / j.stem.2008.01.001 , PMID 18371450 .
- ↑ E. Lefrançais, G. Ortiz-Muñoz, Axelle Caudrillier et al: The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors . In: Nature . tape 544 , March 2017, p. 105-109 .
- ^ H. Hahn et al.: Medical microbiology and infectiology. Springer, 2008, ISBN 978-3-540-46359-7 , p. 40. (online)
- ^ Wilhelm Gemoll : Greek-German school and hand dictionary. Munich / Vienna 1965.