fat transfer with adipose-derived stem and regenerative cells for breast reconstruction

Celution System

Seminar ASPI

25 October 2008

Fat Transfer with Adipose-derived Stem and

Regenerative Cells for Breast Reconstruction

Fat Transfer• Used in reconstruction (to fill defect) and augmentation• Benefit:

– Autologous no rejection, feel more natural– Patient’s preference to reduce the unwanted fat in certain body part as

well as to improve defects in certain body part– No incision scar– Safe in comparison with implant

• Risk: – Fat reabsorption due to necrosis

No more than 3 month tissue survival Produce microcalsification misinterpretation with malignancy in radiology Overcorrection

– Need liposuction• The technique to avoid fat reabsorption:

– Wash the adipose tissue with normal saline– Centrifugation– The addition of nutrients or growth factors– Microinjection of the fat to vascular-rich tissue – Use ADRC

Adipose-derived Stem & Regenerative Cells

• Adult stem cells that have unique properties:– Resides abundantly in adipose tissue the richest

source of stem cells– Differentiate into multiple cell lineages – Extensive self renewal capacity

• Represent tremendous opportunities for treating cardiovascular disease, spine and orthopedic disorders, vascular conditions, reconstructive surgery as well as a variety of other areas of medicine “Regenerative cells”

ADRC vs BM-MSC• Advantages of ADRC

over BM-MSC:– Minimal morbidity upon

harvest– Clinically relevant stem cell

numbers extractable from tissue isolates no need in vitro propagation

– Stem cell frequency is significantly higher in adipose tissue compared with in BM (2% vs 0.002%) 1000 times higher

– Higher proliferation rate than BM-MSC

Strem, Hedrick, Trends in Biotechnology 2005;23(2):64 – 66Fraser, Strem, Nature Clinical Practice Cardiovascular Medicine 2006;3(suppl1):33 – 37

Celution Sytem – Overview• Developed as the 1st bedside device to enable

real-time, adult stem cell processing • This innovative technology automates &

standardized the separation & concentration of a patient’s own (autologous) adult stem & regenerative cells from body fat (adipose) for real-time redelivery to the same patient

• The Celution System makes cells available in about one hour

Celution System

• Celution 800/CRS Device

• Celution 500/CRS Instrument Set

• Celution 805/CRS Kit:– Celution 805/CRS Consumable set– CELASE 835/CRS Reagent – Celution 200/CRS Therapeutic Packs

How it works

Breast Reconstruction

• Breast reconstruction is a physically and emotionally rewarding procedure for a woman who has lost a breast due to cancer or other condition.

• Breast reconstruction is a good option for you if:– You are able to cope well with your diagnosis and treatment – You do not have additional medical conditions or other illnesses

that may impair healing – You have a positive outlook and realistic goals for restoring your

breast and body image

• Breast reconstruction typically involves several procedures performed in multiple stages. It can:– Begin at the same time as mastectomy, or – Be delayed until you heal from mastectomy and recover from

any additional cancer treatments

American Society of Plastic Surgeon

Reconstructive Surgery after Mastectomy

Procedure Advantages General risk Disadvantages

TRAM flapStandard therapy Bleeding, infection,

poor healing of incisions, and

anesthesia risks

-Partial or complete loss of the flap and a loss of sensation at both the

donor and reconstruction site -Produce scar in other place

Latissimus dorsi flap

Standard therapy

-Partial or complete loss of the flap and a loss of sensation at both the

donor and reconstruction site -Produce scar in other place

ImplantNo scar in other place

-Gradual procedure over 4-6 months, tissue expansion

-Capsular contracture firm-Implant Rupture


TRAM flap

Latissimus dorsi flap

Tissue expansion in breast implantation procedure


Reconstructive Surgery after BCT

• No standard therapy. When the defect is small surgeon will perform tissue arrangement. But when the defect is large enough, no standard therapy was established. Implant can only be done in some special case if the implant size and shape suits the defect which is very rare.

• Good opportunity for breast reconstruction with Celution:– No scar only a point of needle inserted– No capsular contracture– No rupture– No thinning compared with absorbed conventional fat graft– Less risks of bleeding, infection and anesthetic risks since it can

be done with local anesthesia– Flatter tummy at a time

Status: enrollment complete

Reconstruction post-partial mastectomy

Endpoints: safety and efficacy

Design: T2 or smaller, 2 yrs post radiation

therapy 21 patients 6, 12 month follow up

Reconstructive Surgery: RESTORE I

Dr. Sugimachi, Dr. KitamuraDr. Sugimachi, Dr. KitamuraKyushu Central HospitalKyushu Central HospitalFukuoka, JapanFukuoka, Japan

RESTORE I TrialPre-OpPre-Op 12 Months Post-Op12 Months Post-Op


6.1

16.0

14.4

0

2

4

6

8

10

12

14

16

PrePre One monthOne month One yearOne year

P ＜ 0.05 P ＝ NS

P ＜ 0.05

mm

Restore I: Breast Tissue Thickness


* ultrasound* ultrasound

Not satisfiedNot satisfied4 (21.1 %)4 (21.1 %)

Satisfied Satisfied 7 (36.9 %)7 (36.9 %)

Very satisfiedVery satisfied8 (42.1 %)8 (42.1 %)

N＝ 19

Restore I: Patient Satisfaction Survey


12 Months

Conclusion• Adipose tissue is the richest source of adult stem cell real-time ADRC-

processing with Celution system• ADRC benefits over MSC in:

– More accessible– 1000-times higher frequency no cell processing needed– Higher proliferation rate

• The limitation of conventional fat transfer can be managed by ADRC-enriched fat transfer: no reabsorption good results, no calcification (safe), do not need overcorrection

• The benefits of ADRC-enriched fat transfer over implant:– More natural– No scar only a point of needle inserted– Safer:

• No capsular contracture• No rupture

– Flatter tummy at a time• Indication of ADRC-enriched fat transfer with Celution system:

– Breast reconstruction post BCT & benign tumour (giant FAM, Phylloides)– Breast augmentation

Every woman is created by God beautifully, “big" or "small" depends on how a woman herself sees in her. If there is any dissatisfaction in her body, why not try to change it? Especially she, who had no choice but had to lose hers because of disease. Thank God, He has created every single cell in the human body to be useful, including restoring her beauty and regaining her confidenceThank

you

Correlation between the ADRC Cell Yield to Processing Volume

• Typical yields are approximately 300,000 cells/g of tissue

Adipose tissue volume (g)

ADRC output

100 30,000,000

150 45,000,000

200 60,000,000

250 75,000,000

How long does it take Celution System to process the ADRCs?

How much graft tissue is needed with the ADRCs?

• Cytori’s research has shown that the typical fat graft is made up of 25 – 30% water.

Comparison of 3 sources of MSC BM UCB AT p

Isolation

Number of CFU-F 83±61 0.002±0.004 557±673 p<0.001

Expansion characteristic

Senescence ratio up to passage 2 23.60% 43.60% 5.60% p=0.02 between AT & UCB

Population doubling numbers lowest highest in the middle

Maximal passage P7 P10 P8

Multilineage differentiation potential

Osteogenic differentiation capacity 78.8% 100% 71.40% Non significant

Adopogenic differentiation capacity 100% 0 94% p<0.01

Chondrogenic differentiation capacity All samples show cartilage-type phenotype with chondrocyte-like lacunae

Differentiation capacities into all three lineages 71.40% 0 71.40%

Multilineage differentiation capacity of BM-CFU-F & AT-CFU-F

towards all 3 lineages 28.60% 89.30% p<0.001

towards 2 lineages 64.20% 7.10% p<0.001

Kern, Stem Cells 2006;24:1294 – 1301

Expression of Surface Proteins of MSCs derived from BM, UCB & AT

fat transfer with adipose-derived stem and regenerative cells for breast reconstruction

Health & Medicine

celution system celution

breast tissue thickness

crs device celution

body fat adipose

reconstruction site

crs reagent celution

tissue isolatesno

fat reabsorption