Adipocytes: more than a tissue filler for bone marrow. Wenyi Lu

1. Adipocytes: more than a tissue filler of
bone marrow
Wen-yi Lu , Kai-yan Liu*
Peking University Institute of Hematology （ PUIH ）
Peking University People’s Hospital
Beijing Key Laboratory of HSCT
Beijing, P.R.China
. 1

2. 2
Background
Delayed hematopoietic recovery is an intractable
problem in patients receiving high-dose chemotherapy
or bone marrow transplantation and it seriously
affects patient survival.
F
Adipocyte-rich marrow

3. 3

4. 4
Background
Naveiras et al. Nature 2009
Zhu et al. Int J Hematol 2013
Snyder et al. Nature 1995
Tripathy et al. Stem Cells Int 2014
Poloni et al. Exp Hematol 2013
Spindler et al. Stem Cell Dev 2014

5. 5
1. To investigate the role of adipocytes in stress
hematopoiesis.
2. To explore the molecular mechanisms
involved in the hematopoietic inhibition
imposed by fatty marrow.
Objective

6. 6
Part-1
PPAR γ agonist rosiglitazone delayed hematopoietic
recovery following myelosuppressive stress

7. 7
Method
4 weeks
5-Fu
2 weeks
BM/Spleen/
PB Cells
CFU assay
Cell phenotype
Normal or Rosiglitazone-
enriched diet
Normal or Rosiglitazone-
enriched diet

8. 8
Part1-Results
1. Rosiglitazone delays hematopoietic recovery after
5-Fu treatment

9. 9
Part1-Results
2. Rosiglitazone treatment maintains LSK while decreases
the proportion of GMP after 5-Fu treatment

10. 10
Part1-Results

11. 11
Part1-Results
3. Rosiglitazone has no effect on HSPC at stress
condition in vitro

12. 12
4. Rosiglitazone-treated stromal cells inhibit myeloid
differentiation from HSPC
from HSPC
Part1-Results

13. 13
Part1-Conclusions
PPARγ agonist rosiglitazone could inhibit the myeloid
differentiation without compromising HSC function,
which may finally lead to a delayed hematopoietic
recovery.
Rosiglitazone inhibit the myeloid differentiation by
promoting adipogenesis rather than directly affecting
HSPC.

14. 14
Part-2
Which molecule mediates the effect of
adipocyte on hematopoiesis?

15. 15
Part2-Results
1. Impact of adipocytic cell on the proliferation
and differentiation of mPB HSPC
The effect of adipocytes on the differentiation of mPB-derived CD34+ HSPC in
transwell coculture system
CD33+(%) CD19+(%) CD7+(%)
CD235a+
(%)
MSC group 84.28±3.89 0.43±0.15* 0.33±0.15 0.80±0.20
Adipocyte
group
77.76±1.40 0.07±0.06* 0.23±0.15 1.16±0.12

16. 2 、 Adipocyte activates adiponectinR1-AMPK signaling
pathway of HSPC
P-AMPK
MSC group Adipocyte group
P-p38

17. Part1-Results
3. The effect of adipocytes on HSPC could be partially
reversed by anti-adiponectin antibody
C
D
38
CD34
CD7
CD19
CD38
MSC group Adipocyte group Adipocyte+anti-APN group

18. 18
Part2-Conclusions
Adipocyte could impair the proliferation and
differentiation of HSPC.
The process may be mediated by adiponectinR-
AMPK signaling pathway.

19. 19
1. Hematopoietic recovery post-chemotherapy is
delayed by rosiglitazone induced bone marrow
adipogenesis.
2. Adiponectin may mediate the adverse effect of
adipocyte on hematopoiesis.
Summary

20. 20
Discussion&Plan

21. Acknowledgements
21
Dr. Weimin Wang
Yao Zhang
Shujuan Wang
Yonghuai Feng
Prof. Kaiyan Liu