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ZITAO LIU, MD, PhD
New Hope Fertility Center, NY, USA
Nuclear Transfer: Clinical Applications
Oct 26, 2017
1. Rejuvenation of aged oocytes 2. Rescue of embryo arrest 3. Offspring for lesbian couple 4. Distant prospect: whole body rejuvenation
Outline:
3
1. Rejuvenation of aged oocytes
Zhang et al 1999
Human GV Transfer
GV Transfer
Jo
hn
Zh
ang
et a
l 19
99
Hu
man
Mo
de
l
12 GVT oocytes 7 matured to MII 4 normal karyotyping
GV from patient (>38 years) Cytoplast from patient (<31 years)
Donor 1
Donor 2
Donor 1 - GV
Donor 2 - cytoplast
Donor 1 GV / Donor 2 cytoplast
Electrofusion
Aged oocyte Reconstituted
in vitro MII GV
Transfer Spindle Nuclear
Transfer Rejuvenated
oocyte
EMBRYONIC DEVELOPMENT FOLLOWED BY RECIPROCAL NUCLEAR TRANSFER
Patient nucleus/ Donor Cytoplasm
Donor nucleus/ Patient
Cytoplasm
D6 D2
2. Rescue of embryo arrest
Current treatment for lesbian:
One of the Donor Sperm
lesbian couple
8
3. OFFSPRING OF LESBIAN COUPLE
Lesbian B
MII spindle
Offspring
Lesbian A
Future Model Donor Sperm
4. Distant prospect: whole body rejuvenation (mice)
CONJOINING YOUNG + OLD MICE:
YOUNG BLOOD REJUVENATES BRAIN AND MUSCLE IN OLD MICE
PARABIOSIS
3. Distant prospect: whole body rejuvenation (human)
REMOVING PLASMA FROM ALZHEIMER’S PATIENTS & REPLACING WITH HEALTHY PLASMA LEADS TO CLINICAL BENEFITS
Nature, Sept 2017
APPLICATION FOR AGING: Somatic Cell Nuclear Transfer (SCNT) to generate patient blastocyst, derive Human Embryonic Stem Cells, differentiate them into Hematopoietic cells. Young blood replacement with own genetic material.
3. Distant prospect: whole body rejuvenation (human)
APPLICATION FOR AGING: Somatic Cell Nuclear Transfer (SCNT) to generate patient blastocyst, derive Human Embryonic Stem Cells, differentiate them into Hematopoietic cells. Young blood replacement with own genetic material.
3. Distant prospect: whole body rejuvenation (human)
Skin cell Enucleated MII
Donor MII
Artificial activation
Parthenote Embryonic Stem Cells
In Vitro Differentiation
hESC-derived hematopoietic cells
ACKNOWLEDGEMENTS
EXTRA SLIDES
Fresh oocyte Normal alignment of MII chromosomes
In vitro aging oocytes Abnormal alignment of MII chromosomes
Aging GV / Fresh ooplast Normal alignment of MII chromosomes
Fresh GV / Aging ooplasm Abnormal alignment of MII chromosomes
Mo
use
Mo
de
l
GV transfer restore normal alignment of MII chromosomes
GV transfer procedure
Hu
i Liu
et
al 2
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3,
Joh
n Z
han
g e
t al
20
15
M
ou
se M
od
el
Nucleus / Cytoplasm
GV transfer oocyte
Maturation rate (%)
Fresh / Fresh 52 98a
Aging / Fresh 35 100 a
Fresh / Aging 37 43 b
Nucleus / Cytoplast
GV transfer oocyte
Normal MII spindle rate (%)
Aging / Fresh 35 91
Fresh / Aging 37 16
Restore meiotic maturation
Restore meiotic spindle structure
Nucleus /
Cytoplasm
GV transfer oocyte
Maturation rate (%)
Fresh / Fresh 52 98a
Aging / Fresh 35 100 a
Fresh / Aging 37 43 b
Nucleus /
Cytoplast
GV
transfer
oocyte
Normal MII
spindle rate
(%)
Aging / Fresh 35 91
Fresh / Aging 37 16
