조혈과 조혈기관

1. 조혈과 조혈기관 Hematopoietic Organs • Yolk sac (2m) • Liver & Spleen (2-7m) • BM (pelvis, sternum, vertebra) • LN & Thymus • Red marrow vs Yellow marrow • Extramedullary hematopoiesis

2. Bone Marrow Structure • Hemopoietic area (stem cell & hemopoietic cell) • Microenvironment(stroma) • Vessel(arteriol, sinus, venule) • Trabecular bone • Paratrabecular area • Fat

3. Aging Process of BM

4. BM RBC release

5. Myeloblast 0.1- 3.5 Promyelocyte 0.5- 5.0 Myelocyte 5.0-20.0 Metamyelocyte 10.0-30.0 Band N 5.0-20.0 Segmented N 7.0-25.0 Eosinophils 0.3- 6.0 Basophils 0 –1.0 Lymphocyte 5.0-20 Monocyte 0-0.2 Proerythroblast 0.5-5.0 Erythroblast 4.0-30 Plasma cell 0.1-3.5 Megakaryocyte 0.1-0.5 Reticulum cell 0.1-2.0 골수의 혈구 분포 (%)

6. 조혈 능력 1일 적혈구 : 20억/kg 혈소판 : 20억/kg 과립구 : 8.5억/kg 소요기간 ( 조혈모세포혈구) 적혈구 : 5일 혈소판 : 7일 과립구 : 10일

8. Stem Cell Sources • BM • PB • Umbilical cord • Fetal liver • Placenta • Yolk sac

9. 조혈모세포 (Stem Cell) CD34+, c-kit+, Sca-1+, Thy-1.1+, CFU-S, CFU-C CFU-GEMM, CFU-GM, CFU-E, CFU-Meg CD34+(CD13+ or -19+) : 5.66% of BM MNC, 1.9% of PB MNC, 1.7% of CB MNC Self-renewal, asymetric division 20 cell divisions produce 106 cells

10. 조혈모세포 분화 단계

11. Pleuripotent stem cell--------CFUGEMM ---- (repopulating cell) -----BFUE-CFUE---------------normoblast ---------RBC ---- CFU-GMEo--CFUGM--CFU-G --myeloblast--neutrophil CFUM--monoblast ---monocyte CFUEo --myeloblast---eosinophil CFUbaso--myeloblast-----basophil ---- CFUMEG----------------------megakaryoblast---platelet ------Lymphoid stem cell---pre-B lympho--B lymphocyte--plasma cell pre-T lymphocyte---T lymphocyte

12. Bone Marrow Microenvironment • Stromal cells • Extracellular matrix • Hemopoietic growth factor,

13. Stromal Cells • Macrophage, fibroblast, endothelial cell, fat cell, dentritic cell • Characters : type IV collagen+, laminin+, vimentin+, CD10+, muscle actin+, Stro-1+

14. Extracellular Matrix Fibronectin Hemonectin Laminin Collagen Proteoglycan(haparan etc)

15. Hemopoietic Growth Factors Multipotent stem cells: IL-3, SCF, IL-1, LIF Myeloid progenitors: GM-CSF, G-CSF, M-CSF, Epo, LIF, SCF, IL-3,-4,-5,-6,-9,-11, TPO T-Lymphoid progenitors : IL-2,-4,-6,-7, B-Lymphoid progenitors:IL-2,-3,-5,-6,-7,-11

16. Stem Cell and Microenvironment

17. Stem Cell and Adhesion Molecules

18. Sources of Hemopoietic Growth Factors Recombinant CSFs Produced by stromal cells, endothelial cells, lymphocytes, fibroblasts, macrophages and epithelial cells.

19. Growth factor receptors and Action Receptors: M-CSFR(c-fms), SCFR(c-kit), IL-R, GM-CSFR, G-CSFR, Epo-R Action: cell division, differentiation commitment , maturation induction , functional activity of mature granulocytes and macrophages, maintaining membrane transport integrity and preventing cell death by apoptosis.

20. Clinical Application of the CSFs • Anemia of chronic renal failure, • Neutropenia • Thrombocytopenia • Following cancer chemotherapy • PBSC collection • ex vivo BM expansion • Stem cell transplantation

21. 조혈능 저하 원인 방사선 조사, 독성 물질: 항암 치료제, 항생제, 항히스타민제, 벤진, 한약제 - 영지, 반하 바이러스 질환 : B형 간염, Parvovirus B19 면역학적 억제 : 재생불량성 빈혈, 혈액 질환 : 백혈병, 암 전이, 골수섬유증

23. Ablazed BM

24. BM Regeneration, day 14

25. 조혈능력의 판단 • CBC : complete blood count • RBC, Hb, Hct, WBC, Platelet, • Neutrophil, Reticulocyte, • Immature reticulocyte • Immature granulocyte

26. 골수 재생을 알 수 있는 방법 • Absolute neutrophil count (ANC) • Immature reticulocyte fraction (IRF) • Hemopoietic precusor cells (HPC)

27. Immature Reticulocyte Fraction • Earlier indicator of BM reconstitution • High, Middle, Low fluorescence ratio • IRF = HFR + MFR =5 - 23% • HFR : < 3.3%

28. Immature Granulocyte Scattergram

29. Chemotherapy후 CD34+, HMFR,Neutrophil 증가 • Neutrophil >500 : auto:17d/ allo :20.5d • HFR >2% : 10d/14d • Ret. >20,000 : 13/18.5

30. 조혈세포가 재생되는 순서시기 • Granulo/Erythroid recovery :1-2 w • Megakaryocyte : 2 w

31. Spleen

32. Splenic Sinusoid • RBC transit • RBC phagocytosis