kÖk hÜcre: solİd organ nakİllerİnde kullanimi...spitzer tr, delmonico f, tolkoff-rubin n, et...
TRANSCRIPT
![Page 1: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/1.jpg)
+
KÖK HÜCRE: SOLİD ORGAN
NAKİLLERİNDE KULLANIMI
Meral Beksaç
Ankara Üniversitesi
Hematoloji Bilim Dalı
Beksac, TİGED 2015, Antalya
![Page 2: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/2.jpg)
+Organ nakilleri
Organ nakillerinde HLA engeli
Uzun süreli immun baskılama
Doku reddi riski
Beksac, TİGED 2015, Antalya
2
![Page 3: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/3.jpg)
Beksac, TİGED 2015, Antalya
3
![Page 4: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/4.jpg)
+
Immunsupresyonrejeksiyon
Immunsupresiflerin yan etkileri:
Diabet
Hipertansiyon
Hiperlipemi
Nefrotoksisite
Fırsatçı enfeksiyonlar
Malign hast(lenfoma)
Beksac, TİGED 2015, Antalya
4
![Page 5: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/5.jpg)
+
Immun tolerans
graft ömrünü uzatıyor:
nasıl kolaylaştırılır?
Beksac, TİGED 2015, Antalya
5
![Page 6: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/6.jpg)
+Tarihçe:
Cosimi AB, Sachs DH. Mixed chimerism and transplantation
tolerance. Transplantation. Mar 27 2004;77(6):943-6.
Beksac, TİGED 2015, Antalya
6
![Page 7: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/7.jpg)
+Kök hücrenin organ nakillerinde
kullanımı
Hematopoietik kök hücre nakli aracılığı ile
immün toleransın oluşturulması
Akut rejeksiyonun engellenmesi
Graft organ işlevlerinin sağlanması
Immunspresif tedavinin süresinin kısaltılması
Mezankimal stromal hücre nakli aracılığı ile
Daha güçlü immünsüpresif etki sağlamak
Nakledilen doku hasarının daha iyi tamiri
Beksac, TİGED 2015, Antalya
7
![Page 8: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/8.jpg)
+
Scandling JD, Busque S, Dejbakhsh-Jones
S, Benike C, Millan MT, Shizuru JA, et al.
Tolerance and chimerism after renal and
hematopoietic-cell transplantation. N
Engl J Med. 2008;358:362–368.
Spitzer TR, Delmonico F, Tolkoff-
Rubin N, et al. Combined histocompatibility
leukocyte antigen-matched donor
bone marrow and renal transplantation for
multiple myeloma with end stage renal disease:
the induction of allograft tolerance
through mixed lymphohematopoietic chimerism.
Transplantation 1999;68:480-4.
Beksac, TİGED 2015, Antalya
8
![Page 9: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/9.jpg)
+
Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined
histocompatibility leukocyte antigen-matched donor bone
marrow and renal transplantation for multiple myeloma with
end stage renal disease: the induction of allograft tolerance
through mixed lymphohematopoietic chimerism.
Transplantation. Aug 27 1999;68(4):480-4.
Multipl Miyeloma tanısı ve son dönem böbrek yetm olan bir
olgudan başlayarak hazırlama rejiminde 2 gün 60 mg/kg
Siklofosfamid ile böbrek nakli sonrası immunsupresif
kesilerek 5 yıldan uzun graft yaşamı elde edilmiş
Beksac, TİGED 2015, Antalya
9
![Page 10: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/10.jpg)
© 1999 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2
Figure 1
COMBINED HISTOCOMPATIBILITY LEUKOCYTE ANTIGENMATCHED DONOR BONE MARROW AND RENAL TRANSPLANTATION FOR MULTIPLE MYELOMA WITH END STAGE RENAL DISEASE: THE INDUCTION OF ALLOGRAFT TOLERANCE THROUGH MIXED LYMPHOHEMATOPOIETIC CHIMERISM.Spitzer, Thomas; Delmonico, Francis; Tolkoff-Rubin, Nina; McAfee, Steven; Sackstein, Robert; Saidman, Susan; Colby, Christine; Sykes, Megan; Sachs, David; Cosimi, A
Transplantation. 68(4):480-484, August 27, 1999.
Figure 1 . Renal function as measured by serum creatinine (serum CRE), whole body cyclosporine levels as measured by a monoclonal antibody assay (CyAlevels), and quantitative urine [kappa] light chain analyses (kappa) during the first 170 days posttransplant. Of note, is that between days +29 and +174, urinary [kappa] light chains were beneath the level of detection (<2.5 mg/100 ml), except for one value of 6.5 mg/100 ml on day +154.
Beksac, TİGED 2015, Antalya
10
![Page 11: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/11.jpg)
© 1999 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 3
Figure 2
COMBINED HISTOCOMPATIBILITY LEUKOCYTE ANTIGENMATCHED DONOR BONE MARROW AND RENAL TRANSPLANTATION FOR MULTIPLE MYELOMA WITH END STAGE RENAL DISEASE: THE INDUCTION OF ALLOGRAFT TOLERANCE THROUGH MIXED LYMPHOHEMATOPOIETIC CHIMERISM.Spitzer, Thomas; Delmonico, Francis; Tolkoff-Rubin, Nina; McAfee, Steven; Sackstein, Robert; Saidman, Susan; Colby, Christine; Sykes, Megan; Sachs, David; Cosimi, A
Transplantation. 68(4):480-484, August 27, 1999.
Figure 2 . Percent overall donor chimerism as well as % donor CD3+ and non-CD3+ T cells as measured by weekly peripheral blood microsatellite variable number of tandem repeat markers. DLI were given on days +57 and +112.
Beksac, TİGED 2015, Antalya
11
![Page 12: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/12.jpg)
+
Bühler LH, Spitzer TR, Sykes M, et al. Induction of kidney
allograft tolerance after transient lymphohematopoietic
chimerism in patients with multiple myeloma and end-stage
renal disease. Transplantation. Nov 27 2002;74(10):1405-9.
Beksac, TİGED 2015, Antalya
12
![Page 13: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/13.jpg)
Beksac, TİGED 2015, Antalya
13
![Page 14: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/14.jpg)
Beksac, TİGED 2015, Antalya
14
![Page 15: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/15.jpg)
Beksac, TİGED 2015, Antalya
15
![Page 16: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/16.jpg)
Beksac, TİGED 2015, Antalya
16
![Page 17: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/17.jpg)
Beksac, TİGED 2015, Antalya
17
![Page 18: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/18.jpg)
Beksac, TİGED 2015, Antalya
18
![Page 19: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/19.jpg)
Beksac, TİGED 2015, Antalya
19
![Page 20: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/20.jpg)
Beksac, TİGED 2015, Antalya
20
![Page 21: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/21.jpg)
Beksac, TİGED 2015, Antalya
21
![Page 22: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/22.jpg)
Beksac, TİGED 2015, Antalya
22
![Page 23: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/23.jpg)
Beksac, TİGED 2015, Antalya
23
![Page 24: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/24.jpg)
Beksac, TİGED 2015, Antalya
24
![Page 25: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/25.jpg)
Beksac, TİGED 2015, Antalya
25
![Page 26: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/26.jpg)
+MGH da aynı dönem nakil olan
haploidentik olgular
Beksac, TİGED 2015, Antalya
26
![Page 27: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/27.jpg)
+Stanford Deneyimi
rATG nin özellikle total lenfoid ışınlama ile birlikte uygulaması regulatory NK
T-cells (CD161+, CD3+) oluşumunu arttırıyor
TLI 800 rad / 10 fraksiyon
rATG 7.5 mg/kg (1.5 mg/kg/g, 5 doz),
Allojeneik hematopoietik kök hücre nakli
Cyclosporine ve MMF
Yüksek donör kimerizmine yol açabilmişÇok az düzeyde GvHD.
Böbrek ve allo HKN birlikte uygulamasına zemin oluşturmuş
Beksac, TİGED 2015, Antalya
27
![Page 28: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/28.jpg)
Beksac, TİGED 2015, Antalya
28
![Page 29: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/29.jpg)
+yıl: 2000-2003
HLA uyumsuz verici,tedavi: T hücre
azaltımı +, 80-100 cGy TLI
Beksac, TİGED 2015, Antalya
29
![Page 30: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/30.jpg)
+yıl:2005-2013, TLI:120 cGy, 5 doz
postop ATG, HLA uygun
Beksac, TİGED 2015, Antalya
30
![Page 31: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/31.jpg)
+Önceki kohort gibi, fark T lenfosit
doz giderek arttırılarak
Beksac, TİGED 2015, Antalya
31
![Page 32: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/32.jpg)
Beksac, TİGED 2015, Antalya
32
![Page 33: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/33.jpg)
+Kimerizm mümkün olabilmiş
38 olgudan hiç birinde graft kaybı yok
HLA uyumlu:
16/22 rejeksiyon olmayan, IS kesilen en az 6 ay kalıcı kimerizm
Haplo uygun:
Daha az, T lenfosit dozu önemli
Beksac, TİGED 2015, Antalya
33
![Page 34: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/34.jpg)
Beksac, TİGED 2015, Antalya
34
![Page 35: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/35.jpg)
Beksac, TİGED 2015, Antalya
35
![Page 36: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/36.jpg)
Beksac, TİGED 2015, Antalya
36
![Page 37: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/37.jpg)
Beksac, TİGED 2015, Antalya
37
![Page 38: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/38.jpg)
Beksac, TİGED 2015, Antalya
38
![Page 39: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/39.jpg)
+MSC uygulaması sonrası in vitro
MNC proliferasyon deneyi
Beksac, TİGED 2015, Antalya
39
![Page 40: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/40.jpg)
+in vivo MSC önce ve sonrası
MNC lerin Donöre karşı sitokin
salgı yanıtı
Beksac, TİGED 2015, Antalya
40
![Page 41: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/41.jpg)
Beksac, TİGED 2015, Antalya
41
![Page 42: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/42.jpg)
Beksac, TİGED 2015, Antalya
42
![Page 43: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/43.jpg)
+MSC uygulaması
Otolog MSC Kemik iliğinden elde ediliyor
Ilk uygulama: böbrek reperfüzyonu sırasında
Ikinci uygulama postop 2.hafta
1-2 milyon MSC/kg iv
Beksac, TİGED 2015, Antalya
43
![Page 44: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/44.jpg)
Beksac, TİGED 2015, Antalya
44
![Page 45: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/45.jpg)
Beksac, TİGED 2015, Antalya
45
![Page 46: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/46.jpg)
Beksac, TİGED 2015, Antalya
46
![Page 47: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/47.jpg)
Beksac, TİGED 2015, Antalya
47
![Page 48: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/48.jpg)
Beksac, TİGED 2015, Antalya
48
![Page 49: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/49.jpg)
Beksac, TİGED 2015, Antalya
49
![Page 50: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/50.jpg)
+MSC uygulaması
allojeneik MSC kemik iliğinden elde edilmiş
Nakilde 3 gün önce başlayarak
Siklofosfamid: 200 mg/g ve PRD 750,500,250 ve 250 mg/g
4. günden itibaren Tacrolismus 0.07-0.08 mg/kg/g (kontrol)
0.04-0.05 mg/kg/g (deney kolu)
MSC ilk uygulama: 5 milyon nakil sırası intraarterial (10ml SF
de 2 dak da inf)
Ikinci uygulama: nakilden 1 ay sonra 2 milyon iv
Beksac, TİGED 2015, Antalya
50
![Page 51: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/51.jpg)
Beksac, TİGED 2015, Antalya
51
![Page 52: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/52.jpg)
Akut rejeksiyon sadece kontrol grubunda tek olgu)
Kimerizm saptanamamışBeksac, TİGED 2015, Antalya
52
![Page 53: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/53.jpg)
1 milyon MSC iliac kemiğe nakil sırası uygulanmışImmunsupresyonda postop 8-10 gün rATG 1.5 mg/kg/g
Beksac, TİGED 2015, Antalya
53
![Page 54: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/54.jpg)
Beksac, TİGED 2015, Antalya
54
![Page 55: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/55.jpg)
Beksac, TİGED 2015, Antalya
55
![Page 56: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/56.jpg)
+Kök hücrenin organ nakillerinde
kullanım amaçları
Hematopoietik kök hücre nakli aracılığı ile
immün toleransın oluşturulması
Akut rejeksiyonun engellenmesi
Graft organ işlevlerinin sağlanması
Immunspresif tedavinin süresinin kısaltılması
Mezankimal stromal hücre nakli aracılığı ile
Daha güçlü immünsüpresif etki sağlamak
Nakledilen doku hasarının daha iyi tamiri
Graft böbrekte fibrozisin engellenmesi
Beksac, TİGED 2015, Antalya
56
![Page 57: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/57.jpg)
+Kök hücrenin organ nakillerinde
kullanım amaçları
Hematopoietik kök hücre nakli aracılığı ile
immün toleransın oluşturulması✔
Akut rejeksiyonun engellenmesi✔
Graft organ işlevlerinin sağlanması✔
Immunspresif tedavinin süresinin kısaltılması✔
Mezankimal stromal hücre nakli aracılığı ile
Daha güçlü immünsüpresif etki sağlamak✔
Nakledilen doku hasarının daha iyi tamiri✔
Graft böbrekte fibrozisin engellenmesi✔
Beksac, TİGED 2015, Antalya
57
![Page 58: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/58.jpg)
+MSC uygulaması ne kadar
güvenilir?
Çeşitli nedenlerle yapılan 1012 MSC tedavi sonrası ikincil
malignite raporlanmamış:
Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW,
Marshall JC, et al. Safety of cell therapy with mesenchymal
stromal cells (SafeCell): a systematic review and meta-
analysis of clinical trials. PloS one. 2012; 7(10):e47559. Epub
2012/11/08.
Franquesa M, Hoogdujin MJ, et al Mesenchymal stem cells in
solid organ transplantation (MiSOT) Fourth Meeting.Lessons
learned from first clinical trials. Transplantation
2013;96(3):324-8. Epub 2013/06/14
Beksac, TİGED 2015, Antalya
58
![Page 59: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/59.jpg)
+MSC hangi immunsupresiflerle
birlikte uygulanabilir?
MSC ler Ciclosporin ve Tacrolismus ile birliktekullanılabilmiş
ATG MSC lerin etkisini azaltıyor
Azathioprin, MSC lerin NK hücreleri tarafından lizisiniönleyebiliyor
Franquesa M, Baan CC, Korevaar SS, Engela AU, Roemeling-van Rhijn M, et al. The effect of rabbit antithymocyte globulin on human mesenchymal stem cells. Transpl Int. 2013; 26:651–658.
Beksac, TİGED 2015, Antalya
59
![Page 60: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/60.jpg)
+MSC ne zaman uygulanmalı?
Peritransplant, postop erken veya
geç dönem mi?
Pefüzyon sırası uygulama etkili, ancak erken postop
uygulama renal fonksiyon üzerine yan etkiye yol açmış
Perico N, Casiraghi F, Gotti E, Introna M, Todeschini M, et al.
Mesenchymal stromal cells and kidney transplantation:
pretransplant infusion protects from graft dysfunction while
fostering immunoregulation. Transpl Int. 2013; 26:867–878.
Beksac, TİGED 2015, Antalya
60
![Page 61: KÖK HÜCRE: SOLİD ORGAN NAKİLLERİNDE KULLANIMI...Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal](https://reader035.vdocuments.pub/reader035/viewer/2022062917/5ed4a8a1bbb05f6cf4450c2d/html5/thumbnails/61.jpg)
+sonuç
Renal transplant modelinde sürekli bir immun tolerans
hematopoietik kök hücre veya mezankimal stromal hücre nakli
ile sağlanabilir
Verici- alıcı arası doku uyumu hala önemli (otolog MSC tercih?)
Aktarılan immun hücrelerin sayısı, uygulama yöntemi henüz
standarta ulaşabilmiş değil,
Beksac, TİGED 2015, Antalya
61