Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants:...
Transcript of Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants:...
![Page 1: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/1.jpg)
Assessing Immune Responses of Stem Cell Transplants
with clinically applicable Imaging Techniques
![Page 2: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/2.jpg)
Stem Cell Tracking Detection of
stem cell apoptosis Immune Cell Tracking
Imaging Approaches
Imaging Stem Cell Transplants:
Assessment of Immune Responses
![Page 3: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/3.jpg)
Imaging Stem Cell Transplants:
Assessment of Immune Responses
Repeatedly image the location(s) and numbers of one or
more specific population(s) of cells in vivo
Allow flexibility to scale across different spatial
resolution levels
Do not significantly perturb the cells while repeatedly
imaging them
Repeatedly image the “status” of stem cells and their
progenies in vivo, including potential interactions with
host cells, such as immune cells
![Page 4: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/4.jpg)
Cellular Imaging Targets / Probes
mRNA
DNA
mRNA
Receptor Mapping
Enzyme Activity:
Inhibition, Conc.,
Synthesis
Accumulation via
AA Transport or
Protein Synthesis Oligonucleotides
mRNA Binding
Reporter Probe Reporter Gene DNA
AAT .
Accumulation via
Phosphorylation
[18F]FDG
mAb,
Fragments Hormones
Drugs and Ligands
Peptides
Accumulation via
DNA-Synthesis
Internalization
Hexokinase
glut 4
![Page 5: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/5.jpg)
Imaging Stem Cell Transplants:
Assessment of Immune Responses
1. In vivo tracking of transplanted stem cells
2. In vivo tracking of immune cells
3. In vivo imaging of tissue regeneration
![Page 6: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/6.jpg)
Clinically applicable labels
for in vivo tracking of stem cells
SPECT and PET Imaging
[18F]-FDG (half life 2 h)
Tc99m HMPAO (half life 6 h)
In-111 Oxine (half-life 2.8 days)
[18F]-Fluoro-3-(hydroxymethyl)butyl]guanine
In-111 Oxine-labeled EPC
acute myocardial infarction
Schaechinger et al, Circulation 2008; Hofmann et al, Circulation 2005; Zhu et al, N Engl J Med 2006
FDG-labeled CD34
enriched BMCs
into LAD
![Page 7: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/7.jpg)
Clinically applicable labels
for in vivo tracking of stem cells
MR Imaging
Gd-Chelates
Iron Oxide
Nanoparticles
SPECT and PET Imaging
[18F]-FDG (half life 2 h)
Tc99m HMPAO (half life 6 h)
In-111 Oxine (half-life 2.8 days)
[18F]-Fluoro-3-(hydroxymethyl)butyl]guanine
Schaechinger et al, Circulation 2008; Hofmann et al, Circulation 2005; Zhu et al, N Engl J Med 2006
Brain trauma
pre
post
Feridex-
labeled
neural
stem
cells
7 days 14 days 21 days
![Page 8: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/8.jpg)
– FDA approved iron supplement
– Mean hydrodynamic diameter: 30nm
– Non-ionic carboxhydrate coating of polyglucose
sorbital carboxymethylether
– r1: 15 mM-1 sec-1
– r2: 89 mM-1 sec-1 at 1.5 Tesla and 37°C2
Khurana et al (Daldrup-Link lab) Nanomedicine under revision
Ferumoxytol (Feraheme™)
Stem Cell Hypertrophy Stem Cell Loss Labeled Stem Cells
![Page 9: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/9.jpg)
Rudelius M, Daldrup-Link HE et al. Eur J Nuc Med & Mol Imag 30: 1038-44
Normal
differentiation
of CM-labeled
stem cells
Normal
differentiation
of unlabeled
controls
Nestin+ stem cell
Nestin+ stem cell
GFAP+ glia cell
GFAP+ glia cell
MAP2+ (neur.cytoskeletton-prot.) neuronal cell
MAP2+ neuronal cell
![Page 10: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/10.jpg)
Differentiation of hESCs into cardiomyocytes
hESCs
Differentiation into cardiomyocytes
Embryoid Bodies
Castaneda et al (Daldrup-Link lab) Pediatr Radiology 41(11): 1384-1392, 2011
![Page 11: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/11.jpg)
Cardiomyocyte protein expression
maintained post ICG-labeling.
Positive staining was observed for:
Connexin43 (a), Wnt8a (b),
Troponin T (c), GATA4 (d), Lin28
(e), TBX5 (f), Actin (g), Islet1 (h).
Scale bar: 100 µm.
Boddington S et al (Daldrup-Link lab) Cell Transplantation 19: 55–65, 2010
![Page 12: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/12.jpg)
Scaffold +
unlabeled cells
Scaffold +
Fe-labeled cells
Scaffold +
Gd-labeled cells
Chondrogenic differentiation of Fe-labeled hMSC
Henning T et al (Daldrup-Link lab) Contr Media Mol Imaging 4(4): 165-173
![Page 13: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/13.jpg)
Henning T, Gawande R (Daldrup-Link lab), Molecular Imaging 11(3):197-209, 2012
In vivo diagnosis of stem cell proliferation vs apoptosis
Day 0 Week 2 Week 4 Week 8
Prussian Blue Anti-CD44
VIA
BL
E
Prussian Blue Anti-CD44
AP
OP
TO
TIC
Matrix associated stem cell implants
in osteochondral defects
![Page 14: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/14.jpg)
Imaging Stem Cell Transplants:
Assessment of Immune Responses
1. In vivo tracking of transplanted stem cells
2. In vivo tracking of immune cells
3. In vivo imaging of tissue regeneration
![Page 15: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/15.jpg)
MR Imaging
Gd-Chelates
Iron Oxide
Nanoparticles
SPECT and PET Imaging
[18F]-FDG (half life 2 h)
Tc99m HMPAO (half life 6 h)
In-111 Oxine (half-life 2.8 days)
[18F]-FHBG
Tracking EpCAM-targeted NK cells
-> EpCAM-positive cancer
CD 57 stain
Fe-stain
CD 57
pre
24 h
Cancer Immunotherapy
Meier R (Daldrup-Link lab), Magn Res Med 65(3):756–763, 2011
Clinically applicable labels
for in vivo tracking of leukocytes
![Page 16: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/16.jpg)
MR Imaging of Macrophage Migration into MASI
Khurana A (Daldrup-Link lab), Radiology 264(3):803-11, 2012
![Page 17: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/17.jpg)
Monocyte
Macrophage Imaging
Reticuloendothelial System Bone Marrow
Progenitor cell
Monocyte
Liver Spleen Lymph Nodes
MØ MØ MØ
MØ
i.v. injection
of iron oxide
nanoparticles
![Page 18: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/18.jpg)
Monocyte
Macrophage Imaging
Reticuloendothelial System Bone Marrow
Progenitor cell
Monocyte
Spleen Lymph Nodes
MØ MØ MØ
15-60 min
post USPIO
MØ
Liver
![Page 19: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/19.jpg)
Monocyte
Macrophage Imaging
Reticuloendothelial System Bone Marrow
Progenitor cell
Monocyte
Liver Spleen Lymph Nodes
MØ MØ MØ
60 min post
USPIO
MØ
![Page 20: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/20.jpg)
Monocyte
Macrophage Imaging
Reticuloendothelial System Bone Marrow
Progenitor cell
Monocyte
Liver Spleen Lymph Nodes
MØ MØ MØ
Stem Cell
Transplant
MØ
![Page 21: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/21.jpg)
Monocyte
Macrophage Imaging
Reticuloendothelial System Bone Marrow
Progenitor cell
Monocyte
Liver Spleen Lymph Nodes
MØ MØ MØ
Liver
MØ
Stem Cell
Transplant
![Page 22: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/22.jpg)
No Fe IV ferumoxytol labeled bone marrow macrophages
2a. 2b. 2c.
Week 2 Week 4 Stem Cell Implant
APOPTOTIC
VIABLE MASI
In vivo tracking of macrophages
Stem Cell Implant
Khurana A (Daldrup-Link lab), Radiology 264(3):803-11, 2012
![Page 23: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/23.jpg)
wk 0 wk 0 wk 2 wk 2 wk 4 wk 4 0
5
10
15
20
25
VIABLE APOPTOTIC
SN
R
In vivo tracking of macrophages
Khurana A (Daldrup-Link lab), Radiology 264(3):803-11, 2012
![Page 24: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/24.jpg)
MR Imaging
Gd-Chelates
Iron Oxide
Nanoparticles
SPECT and PET Imaging
[18F]-FDG (half life 2 h)
Tc99m HMPAO (half life 6 h)
In-111 Oxine (half-life 2.8 days)
[18F]-Fluoro-3-(hydroxymethyl)butyl]guanine
18F-FDG-labeled leukocytes,
Normal scan
Dumarey et al, J Nucl Med 2006
18F-FDG-labeled leukocytes
-> infected aortic valve
Clinically applicable labels
for in vivo tracking of leukocytes
![Page 25: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/25.jpg)
PET Reporter Gene Imaging for Tracking CTL
[18F]FHBG
9-[4-[18F]-Fluoro-3-
(hydroxymethyl)butyl]guanine
![Page 26: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/26.jpg)
PET Reporter Gene Imaging for Tracking CTL
Tumor accumulation of CTL
in recurrent Glioma
pre
3d after CTL, 2 h post [18F]FHBG
9-[4-[18F]-Fluoro-3-
(hydroxymethyl)butyl]guanine
courtesy of S. Gambhir, Stanford University
![Page 27: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/27.jpg)
Imaging Stem Cell Transplants:
Assessment of Immune Responses
1. In vivo tracking of transplanted stem cells
2. In vivo tracking of immune cells
3. In vivo imaging of tissue regeneration
![Page 28: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/28.jpg)
Imaging Cartilage Regeneration
4 years after matrix associated chondrocyte transplant:
Successful cartilage repair
PDW 3200/30 T1 map
dGEMRIC 490/13
Trattnig et al, Radiology 2011, 260: 332
T2 map,
SE 2700/10-20
Anatomy
GAG content proton content
![Page 29: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/29.jpg)
Imaging Tissue Regeneration
reduced
FOV
anatomic
T2 scan
ADCiso Color FA Fibers
MR Tractography
Traumatic Cord Injury
normal
Injury site
courtesy of Greg Zaharchuk, Stanford University
Normal Volunteer
![Page 30: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/30.jpg)
What comes next along the path?
![Page 31: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/31.jpg)
PET
MR Imaging
Radiography
Optical Imaging
SPECT
Fusion
Scans
![Page 32: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/32.jpg)
Clinically applicable techniques
for imaging stem cell transplants
& related host immune responses
are readily available
TAKE HOME MESSAGE
![Page 33: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/33.jpg)
Translational Tumor and Stem Cell Imaging Lab,
Lorry Lokey Stem Cell Research Building @ Stanford
Grant Support:
NIH/NIAMS 2R01AR054458-05, R21AR059861
Stanford Cancer Institute, (CIRM 2007-09)
Aman Khurana
Hossein Nejadnik
Fanny Chapelin
Olga Lenkov
Su Hyun Hong
Jessica Donig
Rakhee Gawande
Qiaoyun Shi
Celina Anasari
Christopher Klenk
Beverly Newman
Richard Barth
Amy Morris
Jennifer Vancil
Jianghong Rao
Deju Ye
Laura Pisani
Brian Rutt
R. Paulmurugan
Nikita Derugin
Greg Zaharchuk
Deqiang Qiu
Michael Moseley
Andrew Quon
John Ronald
Sanjiv Sam Gambhir
Stanford Radiology Institute for Stem Cell
& Regenerative Medicine
Charles Chan
Jeong Hyung
Michael Longaker
Electrical Engineering
Sungmin Lee
Dwight Nishimura
Northwestern University
Thomas Meade
![Page 34: Assessing Immune Responses of Stem Cell Transplants with ...€¦ · Imaging Stem Cell Transplants: Assessment of Immune Responses Repeatedly image the location(s) and numbers of](https://reader034.fdocuments.net/reader034/viewer/2022042303/5ece04a8207bab2154163fad/html5/thumbnails/34.jpg)
Thank you!
Daldrup-Link Lab, Molecular Imaging Program @ Stanford
Translational Tumor and Stem Cell Imaging Lab,
Lorry Lokey Stem Cell Research Building @ Stanford