Current Controversies of Stem Cell

Therapies

Professor Minghao Zheng, MD, PhD, FRCPath, FRCPA

Medical School

Associate Dean, Faculty of Health and Medical Sciences,

The University of Western Australia, Perth, WA, 6009

Minghao.zheng@uwa.edu.au

Declaration of Interest

I declare that in the past three years I have:

• held shares in Orthocell Ltd;

• received institutional support from NHMRC, ARC

Signed: minghao zheng

• What are the controversies surrounding

stem cell therapies?

• How do we define the boundaries of

practice?

• Is there a place for stem cell therapy in

Orthopaedics

Life starts with blastocyte stem cells

Inner cluster mass (ICM) of blastocytes

Stem cell therapy is not new

• First cellular therapy in

1959

• Dr Georges Mathé

• Conducted first bone

marrow cell therapy on five

Yugoslavian nuclear

workers whose own

marrow had been damaged

by irradiation

E Donnall Thomas

• Development of bone marrow

transplantation as a treatment

for leukaemia;

• In 1990, he shared the Nobel

Prize in Physiology or

Medicine with Joseph E.

Murray for the development of

cell and organ transplantation.

Induced Pluripotent Stem Cells (iPSC)

Turning Back the Cellular Clock: A

Farewell to Embryonic Stem Cells?

Shinya Yamanaka 2012

Stem cells – the public perception

Stem cells are not a miracle

There is “emerging” evidence it may work

to repair corneas to prevent the most

common causes of blindness. It is looking

promising in cerebral palsy, to treat lung

damage in premature babies and

osteoarthritis among many others.

But for all the other ailments, from anti-

ageing to autism, spinal cord injury to

Alzheimer’s disease, the consensus from

Australia’s leading experts is; “there is not

a shred of evidence it works”.

http://www.abc.net.au/radionational/programs/backgroundbriefing/hallmarks-of-quack-medicine-in-fatal-stem-cell-treatment/7630288

Stem cells are required more

research, We don’t want to

see…

• Lack of sufficient pre-clinical evaluation;

• Exploitation of regulatory loopholes;

• Lack of research and clinical evidence;

• Overpromise;

Shapiro et al, A Prospective, Single-Blind, Placebo-

Controlled Trial of Bone Marrow Aspirate Concentrate for

Knee Osteoarthritis. Am J Sports Med. 2016 Aug 26

Patients experienced a similar relief of pain

in both BMAC- and saline-treated arthritic

knees !

Common adverse events of stem cells therapies

Same day procedure is

relatively safe (SD);

Fat oil from adipose tissue

cause pain (AD);

Cultured MSCs promote

disease progression (CE).

Australia Research Council launches

roadmap for Australian stem cell science

Position statement 21 March 2016

Recommendations

• Clinicians to establish a boundary of clinical

practice;

• Improve community engagement and

awareness of stem cell research and

therapy;

• Improve patient access to clinical trials;

• Facilitate cross disciplinary collaboration

Liposuction stem cell therapy Stem cell clinics

• What are the controversies surrounding

stem cell therapies?

• How do we define the boundaries of

practice?

• Is there a place for stem cell therapy in

Orthopaedics

• MACI - Autologous chondrocyte

implantation for cartilage

injuries;

• ATI - Autologous tendon cell

injection for tendinopathy and

tear.

Am J Sport Med 2010 38:1259

http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm533153.htm

Matrix induced ACI (MACI)Cell-scaffold construct

GMP Lab

30 minutes

surgery;

small incision

or

arthroscope

Zheng et al 2006

SUMMIT Trial

• MACI - Autologous chondrocyte

implantation for cartilage

injuries;

• ATI - Autologous tendon cell

injection for tendinopathy and

tear.

Substitution of tendon cell by

injection to central tear site

improve tendon healing in

tendinopathy.

Research Evidence of ATI

Chen et al 2007; 2011; Wu et al 2011; Zheng et al Science (supplementary) 2012

Feridex cell tracking within the tendon

J Chen, M.B.Ph.D.et al TISSUE ENGINEERING: Part A 17:15, 2011 Cover page

BMJ 2013

AJSM 2014

AJSM2013

Clinical Evidence: level III/IV

Indication Expansion = 376 cases

Gluteal Tendon =17

Patellar Tendon = 27

Hamstring Tendon = 9Rotator Cuff =36

Achilles Tendon =17

Tennis elbow = 52

Adductor and Biceps = 3

• Post-market surveillance indicating that

70.7% of patients were satisfied with the

outcome of their Ortho-ATI® treatment

(including both the resolution of symptoms

and ability to resume daily activities).

Level II Clinical Evidence: Outcome of ATI

RCT study in Holland

Level II Clinical evidence

Comparison of ATI with surgery in patients

with chronic resistant lateral epicondylitis

(ACTRN12616000458437p),

Rest

Physio-therapy

Injection

Cell

Surgery

Treatment principle and algorithm of tendinopathy

Pathogenesis Treatment principle

Overuse Avoid re-injury

Angiofibroblastichyperplasia

Mechanical induction ofintrinsic repair

Degenerative change of tendon cell & matrix

Control of pain

Matrix breakdown& Fatigue healing

Substitution of tendon progenitor cells for

tendon repair

Structural changes with mechanical failure

Correction of biomechanics & decompression

Bhabra et al JOSM 2016

Take home messages

- Clinicians need to define their boundary of

practice for stem cell therapy;

- Any stem cells injection into joint have shown

not working;

- Autologous chondrocyte implantation works for

localised cartilage injury and is an FDA

approval cellular product;

- Autologous Tenocyte Injection is working but

need higher level of clinical evidence (level II

and above).

THANK YOU