Hematopoietic stem cell

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All blood cells develop from progenitor cells and at the beginning of hematopoiesis there are hematopoietic stem cells.

With haematopoietic stem cell or hematopoietic stem cell , the first is referred to from the parenchyma derived colorless blood cell of the post-embryonic bone marrow as well as the colorless blood cell, the embryonic liver, spleen and bone marrow of the embryonic. It is the starting point for the entire formation of new cells in the blood and the immune system ( hematopoiesis ). Blood stem cells are cells from the bone marrow or umbilical cord blood that are used to treat leukemia in a transplant (→ stem cell transplant ).

History of the stem cell 1868 to approx. 1912: Unitarianism

Hematopoietic stem cell 1874 in the native preparation in the embryonic liver resp. postembryonic bone marrow

Until the 19th century, humoral pathology only knew blood as “juice”. In 1844 Johannes Müller (1801–1858) referred to the blood corpuscles as cells and already postulated the conversion of colorless cells to colored ones in the lymph. Ernst Heinrich Weber (1795–1878) saw the nucleated blood cells in the embryonic liver for the first time in 1845 and Albert von Kölliker (1817-1905) considered these embryonic red nucleated blood cells (today's erythroblasts) in the liver to be descendants of white blood cells. Until 1868 the question of postembryonic blood formation did not arise because blood cells were generally considered to be descendants of embryonic cells from the mesenchyme or the vascular endothelium. On October 10, 1868, at the Königsberg Pathological Institute, the bone marrow was described as a blood-forming organ with its hematopoietic "lymphoid marrow cell" by Ernst Neumann (1834-1918) (Neumann 1868, 1869) and confirmed a little later by Giulio Bizzozero (1846-1901). The original communication from October 10, 1868 is posted by Ernst Neumann (pathologist) . Three days after the first publication, Ernst Christian Neumann, as head of the institute for the Association for Scientific Medicine founded by Hermann von Helmholtz (meeting report of October 13, 1868), specified his ideas about the "lymphoid blood cell" that is present in the extrauterine and that can also be regenerated in adulthood:

“Not only can a permanent new formation of blood cells be asserted with certainty for the growth period when the blood mass increases proportionally to the body mass, but it is also highly probable a priori that this new formation process will continue in the adult body, since life is the individual blood cells is probably only a limited one…! ”…“ Throughout life there is a continuous introduction of marrow cells into the blood, and these immigrated cells are transformed into colored cells (nucleated red blood cells) in the vessels of the marrow. This metamorphosis still takes place within the bones, since as a rule only finished blood cells are found in the vein blood. ” (Original text of October 13, 1868 in the Scientific Medical Association). It goes on to say: The conclusion is justified that throughout life there is a continuous conversion of lymphoid-like cells into colored blood cells in the bones.

According to Neumann, a similar blood cell formation takes place in the embryonic liver, spleen and embryonic bone marrow as well as postembryonally exclusively in the bone marrow. The first recordings of this colorless blood cell with transition to the erythroblasts date back to 1874. In the microscopic picture of a native preparation in 1874, Ernst Neumann showed the transformation of a lymphoid marrow cell (today's hematopoietic stem cell) into a nucleated colorless erythroblast. For Neumann, this development took place identically in the embryonic liver and in the postembryonic bone marrow.

In 1878, in connection with the first description of the diseased marrow cell (today's myeloid leukemia), Neumann also had leukocytopoiesis developed from the "lymphoid marrow cell". The original tissue is the parenchyma.

"Neumann and Bizzozero reported observations and drew conclusions that were so revolutionary that they were not accepted." "Despite all the opposition, however, within two decades, Neumann's discovery was a scientific axiom! The brilliance of the truth may first be blinding, but ultimately it supersedes all artificial illuminators. "

In the following 50 years a battle broke out over the origin of the stem cell. The Unitarian point of view implied that all blood cell lines develop from a postembryonic existing haematopoietic stem cell. "All forms of the same [leukocytes] can be traced back to a common stem cell that is also always present in the extrauterine".

His theory of blood formation between 1868 and 1912 is shown in the accompanying table, which was presented in 1994 for the 450th anniversary of Albertus University.

Unitarianism: All blood cells, including lymphocytes, are derived postembryonally from a hematopoietic stem cell in the bone marrow

The Unitarians Alexander A. Maximow (1874–1928) (“Large lymphocyte” as “stem cell” - June 1, 1909 meeting of the Berlin Hematological Society, p. 297) from St. Petersburg, Max Askanazy , Königsberg and Geneva agreed with this opinion , Franz Weidenreich (1873–1948), Wera Dantschakoff-Grigorewski (born 1879), Ernst Grawitz (1860–1911), Hans Hirschfeld (1873–1944) and Artur Pappenheim (1870–1916), the latter in his and Grawitz founded in 1908 the "Berlin Hematological Society" (1908). Also to be mentioned are S. Mollier, Adolfo Ferrata (1880–1946) and Georg Eduard von Rindfleisch (1836–1908). In the dispute over the hematopoietic stem cell, however, the dualists prevailed: a stem cell created once in the embryonic period differentiates into several different blood cell rows after birth. The most assertive dualist was Nobel Prize laureate Paul Ehrlich (1854–1915) alongside Wilhelm Türk (1871–1916) from Vienna and Otto Naegeli (1871–1938) from Switzerland. His work: Blood Diseases and Blood Diagnostics 2nd Edition 1912, became the standard work in German-speaking countries. Here Naegeli goes "strictly to judgment" with the Unitarians. The dualistic position of Paul Ehrlich on several embryonic stem cells is shown in the figure.

Dualism: According to P. Ehrlich, the blood cell rows are derived from the embryonic stem cell

In preparation for the 1st International Hematology Congress at the Medical Clinic of the Berlin University, Wilhelm Türk summed up: “Just as a chimpanzee does not become a human, a 'lymphocyte' (postembryonic large lymphocyte stem cell in the bone marrow, author) does not become a polymorphonuclear granulocyte . ” As a result of this dispute, the“ Berlin Hematological Society ”built up by Unitarians fell into a crisis after 4 years (1912) and so lost its influence that it“ fell asleep ”. (Voswinckel 1987).

History of the stem cell from around 1912 to the middle of the 20th century: dualism

With the end of the “Berlin Hematological Society”, there was a tendency towards nation-state thinking in Germany: Artur Pappenheim resisted a call to the question of guilt for the outbreak of war and was transferred to a Russian typhus hospital. Infected by this disease, he died in 1916. Georg Friedrich Nicolai (1874–1964) was shouted at by “German-thinking students” after the First World War and emigrated to South America in 1922 (all references from Voswinckel 1987). In 1912 Neumann attempted to mediate by demanding a stem cell culture to clarify the disputed question , “which ROBERT KOCH taught to do with bacteria, namely to isolate the individual cells and to follow their life processes [in a pure culture] in vitro for a long time . ” But he was not heard. With the death of Artur Pappenheim, the emigration of Georg Nicolai and later George Rosenow (1886–1985), Georg Klemperer (1865–1946) and Selma Meyers (1881–1959), an entire era of excellent German hematology researchers came to an end. Stem cell research was now carried out more in the Anglo-American region ( Florence Sabin , 1871–1953) and knowledge of the former achievements of Königsberg and Berlin was forgotten.

From 1968: the stem cell success story

On the 100th anniversary of the 1868 stem cell description, G. Rosenow took up the topic of the history of the stem cell again. The unitarianism-dualism dispute was in favor of unitarianism, i.e. H. the pluripotent blood stem cells that existed in the bone marrow well into old age. The main researchers were E. Undritz and Karl Rohr. The proof came about the implementation of cultures, which were already introduced in the time of A. Maximow (1928) and continued through Alexis Carrel (1873-1944), Donald Metcalf (born 1929) up to the so-called "mixed colonies" from Hans G. Messmer (born 1941) to Axel A. Fauser (born 1948).

The further history was dealt with through the popular scientific biography Neumann-Redlin von Medings , the dissertation based on it by Yvonne Klinger and the scientific work of Herbert Neumann (Bochum). Initiated by these publications, a return to Prussian stem cell research began in the USA. The main researchers were J. Dreyfus, JM Yoffrey, M. Wintrobe, M. Tavassoli, M. Ramalho-Santos and Holger Willenbring as well as AH Mähle, R. Dinser and NH Zech.

"Stem cell" nomenclature

The biologist Ernst Haeckel (1834-1919) (zoologist and philosopher) used the term "stem cell" for the first time in 1868, based on the family trees of genealogy . Theodor Boveri (1862–1915), (biologist), adopted this name in 1892. For the hematopoietic stem cell, which has been called "lymphoid marrow cell" since its first description in 1868, or many other names with regard to the "colorless lymphoid cell", Artur Pappenheim in Berlin in 1896 took over the name "stem cell" from Theodor Boveri and Valentin Häcker (1864–1927), followed by Alexander Maximow (1909) and Ernst Neumann (1912) (Ramalho and Willenbring).

Future of the stem cell

The hematopoietic stem cell serves as a starting point for new branches of research in theoretical and clinical medicine: hematology , immunology , oncology , pathology , genetics and transplant medicine as a field of regenerative medicine (autologous and allogeneic transplantation).

Web links

literature

  • M. Askanazy: Ernst Neumann. In: Zbl. f. General Path. u. Path. Anat. 29, 1918, pp. 409-421.
  • Giulio Bizzozero: Sulla funzione ematopoitica del midollo delle ossa. In: Gazz. Med. Ital. Lombardia. Volume 28, No. 46, 1869, p. 381.
  • Theodor Boveri: Fertilization. In: Results of anatomy and history of development. (Wiesbaden). Volume 1, 1892, pp. 386-485.
  • C. Dreyfus: Some milestone in the history of hematology. Grune u. Stratton, New York / London 1957.
  • AA Fauser, HA Messner: Identification of megakaryocytes…. In: Blood. Volume 53, 1979, pp. 1023-1027.
  • AA Fauser et al: Cytotoxic T-cell clones derived from pluripotent stem cells (CFU-GEMM) of patients with Hodgkin's lymphoma. In: Blood. Volume 60, No. 6, 1982, pp. 1317-1320.
  • Valentin Haecker: The core division processes in mesoderm and endoderm formation in Cylops. In: Arch. Mikr. Anatomy. Volume 39, 1892, pp. 556-581.
  • RA v. Kölliker: About the blood cells of a human embryo and the development of blood cells in mammals. In: Z.rat.Med. Volume 4, 1846, pp. 112-159.
  • S. Mollier: Blood formation in the embryonic liver of humans and mammals. In: Arch.f. Micr. Anat. Volume 74, 1909, p. 474.
  • E. Neumann: About the importance of the bone marrow for blood formation. In: Centralblatt für die Med. Wissenschaft. Volume 44, 1868, p. 689.
  • E. Neumann: About the importance of the bone marrow for blood formation. A contribution to the development business. of blood cells. In: Archiv f. Medicine. Volume 10, 1869, pp. 68-102 (Wagner's archive)
  • E. Neumann: A case of leukemia with disease of the bone marrow Appendix: Salkowski: Chemical investigations of the leukemic marrow (7/28/69). In: Archives of Medicine. (Wagner's archive). Volume XI, 1871, pp. 1-15.
  • E. Neumann: New contributions to the knowledge of blood formation. In: E. Wagner's archive of medicine. Volume XV, 1874 with illustration (native preparation) from nucleated red blood cells to nucleated erythrocytes (blood and pigments, pp. 63-92)
  • E. Neumann: The law on the spread of the yellow and red bone marrow. In: Centralblatt für die Med. Wissenschaft. Volume 18, 1882, pp. 321-323.
  • E. Neumann: About the development of red blood cells in the newly formed bone marrow. In: Virchow's archive. Volume 119, 1890 (blood and pigments, pp. 201–211)
  • E. Neumann: Hematological Studies III. Leukocytes and leukemia. In: Virch. Arch. Volume 207, 1912, pp. 379-412.
  • E. Neumann: New contribution to the knowledge of the embryonic liver. In: Arch.f.mikr. Anat. Volume 85, Abt. I, 1914, pp. 480-520.
  • E. Neumann: Blood and Pigments. Jena Gustav Fischer, 1917.
  • E. Neumann-Redlin von Meding: Ernst Chr. Neumann (1834-1918); The description of the functional morphology of the bone marrow at the Pathological Institute in Königsberg and its influence on the hematology of the 19th century. In: Yearbook of Albertus Univ. Königsbg. Volume 29, 1994, pp. 425-437. and D. Rauchning et al. (Ed.): The Albertus University of Königsberg and its professors. Duncker & Humblot, Berlin 1995.
  • E. Neumann-Redlin von Meding: The pathologist E. Neumann and his contribution to the foundation of hematology. In: Munich series of publications. Society. Business d. Med. Volume 18, Demeter-Verlag, Munich 1987.
  • G. Beef: About bone marrow and blood formation. In: Arch.mikr.Anat. Volume 17, 1880, pp. 1-11, 21-42.
  • Wilhelm Türk: Critical remarks on blood cell formation and naming. In: Folia hemat. Volume 2, 1905, pp. 231-247.
  • Ernst Heinrich Weber : About the importance of the liver for the formation of blood cells for the embryos. In: Z.rat.Med. Volume 4, 1845, pp. 160-167.
  • Franz Weidenreich: About the nature and importance of the "large mononuclear leukocyte" Ehrlichs. In: 3rd meeting of the Berlin Hematological Society on March 5, 1911. pp. 215–230.
  • M. Wintrobe: Hematology, the Blossoming of a Science; a story of inspiration and effort. Lea & Febiger, Philadelphia 1985.
  • NH Zech, A. Shkumatov, S. Koestenbauer: The magic behind stem cells. In: Journal of Assisted Reproduction and Genetics. Volume 24, No. 6, 2007, pp. 208-214.

Individual evidence

  1. ↑ Yvonne Klinger: About the discovery of the hematopoietic function of the bone marrow and the postulate of the stem cell. From Ernst Neumann's hypothesis to the experim. Proof. Inaugural dissertation. Bochum 1992.
  2. ↑ E. Neumann: About the importance of the bone marrow for blood formation. In: Arch. D. Heilkunde. 10, 1869, pp. 68-102.
  3. ^ E. Neumann: New contributions to the knowledge of blood formation. In: E. Wagner's archive of medicine. Volume XV, 1874, Fig. 6fß with transition to erythroblasts 6fa.
  4. ↑ M. Askanazy: Ernst Neumann. In: Verh. Dt. Path.Ges. 28, 1935, pp. 363-372. Here p. 369: “Neumann explained on the frog that these stem cells, the 'lymphocytes' in the broader sense of the word, i.e. H. are to be assigned to the unstained parenchymal cells of the blood formation tissue. There is no question of the endothelium or the reticular cells. "
  5. ↑ M. Wintrobe: Hematology, the Blossoming of a Science; a story of inspiration and effort. Lea & Febiger, Philadelphia 1985.
  6. ^ M. Tavassoli: Bone Marrow: The Seebed of Blood. from MM Wintrobe: Blood, pure and eloquent. sh.5; Mc.Graw-Hill Book Company Leo Febiger, Philadelphia 1980.
  7. ↑ E. Neumann: Hematological Studies III. Leukocytes and leukemia. In: Virch. Arch. 207, 1912, pp. 379-412.
  8. ^ E. Neumann-Redlin von Meding: Ernst Chr. Neumann (1834-1918); The description of the functional morphology of the bone marrow at the Pathological Institute in Königsberg and its influence on the hematology of the 19th century. In: Yearbook of Albertus Univ. Königsbg. Volume 29, 1994, 425-437. and D. Rauchning et al. (Ed.): The Albertus University of Königsberg and its professors. Duncker & Humblot, Berlin 1995.
  9. ^ HA Neumann, Y. Klinger: Bone marrow and stem cells. The battle for the basics of hematology. (= Ex libris Roche. Volume 1). Blackwell Verlag, Berlin 1994, p. 107.
  10. ↑ Wilhelm Türk: Critical remarks on blood cell formation and naming. In: Folia hemat. 2, 1905, pp. 231-247.
  11. ↑ Peter Voswinckel: 50 years of the German Society for Hematology and Oncology. Wuerzburg 1987.
  12. ↑ Peter Voswinckel: 50 years of the German Society for Hematology and Oncology. Wuerzburg 1987.
  13. ↑ E. Neumann: Hematological Studies III. Leukocytes and leukemia. In: Virch. Arch. 207, 1912, pp. 379-412.
  14. ^ G. Rosenow: Ernst Neumann. His Significance in Todays Hematology. In: Kargers Gazette. 15, 1967.
  15. ^ HA Neumann, Y. Klinger: Bone marrow and stem cells. The battle for the basics of hematology. (= Ex libris Roche. Volume 1). Blackwell Verlag, Berlin 1994, pp. 130-148.
  16. ↑ Yvonne Klinger: About the discovery of the hematopoietic function of the bone marrow and the postulate of the stem cell. From Ernst Neumann's hypothesis to experimental proof. Inaugural dissertation. Bochum 1992.
  17. ↑ M. Wintrobe: Blood, pure and eloquent; a story of discovery of people and of ideas. Mc. Graw Hill Book Company, Leo & Febiger Philadelphia 1980.
  18. ↑ M. Tavassoli: Bone Marrow: The Seebed of Blood from MM Wintrobe: Blood, pure and eloquent. sh.5; Mc.Graw-Hill Book Company Leo Febiger Philadelphia 1980.
  19. ^ Miquel Ramalho-Santos, Holger Willenbring: On the Origin of the “Stem Cell”. In: Cell Stem Cell. 1, July 2007, pp. 35-38.
  20. ↑ Andreas-Holger Mæhle: Ambiguous Cells: the Emergence of the stem cell concept in the nineteenth centuries. In: Notes Rec. R. Soc. doi: 10.1098 / rsnr.2011.0023
  21. ↑ Ricarda Dinser: The contribution Artur Pappenheim hematology around the turn of the century. Dissertation. Ruhr University Bochum, 2001. (PDF)
  22. ↑ NH Zech, A. Shkumatov, p Köstenbauer: The magic behind stem cells. In: Journal of assisted reproduction and genetics. Volume 24, Number 6, June 2007, pp. 208-214, doi: 10.1007 / s10815-007-9123-z . PMID 17385026 , PMC 3454971 (free full text) (review).
  23. ↑ A. Pappenheim: About the development and formation of the erythroblasts. In: Arch. Path. Anat. U. Physiology Clinical Medicine. Volume 145, No. 3, 1896, pp. 587-690.
  24. ^ Miquel Ramalho-Santos, Holger Willenbring: On the Origin of the “Stem Cell”. In: Cell Stem Cell. 1, July 2007, pp. 35-38.