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Journal of Transmitted Diseases and Immunity
ISSN: 2573-0320
Page 83
Volume 4
May 10-11, 2018
Frankfurt, Germany
Immunology Research 2018
Tissue Science 2018
JOINT EVENT
2 2
n d
E d i t i o n o f I n t e r n a t i o n a l C o n f e r e n c e o n
Immunology and
Evolution of Infectious Diseases
&
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t h
E d i t i o n o f I n t e r n a t i o n a l C o n f e r e n c e o n
Tissue Engineering and
Regenerative Medicine
I
t is not unusual for animal models of disease to inaccurately
predict clinical outcome of clinical studies. One such example
is stem cell therapy for stress urinary incontinence (SUI)
where preclinical studies report almost complete remission
of symptoms, whereas clinical studies report only around 50%
remission in 50% of patients. The answer is most likely explained
becauseanimalmodels (whichcreateacuteSUI in relatively young
animals) do not represent the most common clinical scenario
where SUI is most common as a chronic disease in peri/post-
menopausal women with co-existing risk factors such as obesity
and type-2 diabetes. To better predict the effects of cell therapy
for UI, we developed a cynomolgus monkey model of urinary
incontinence (surgical nerve and muscle damage to the urinary
sphincter complex) that reproduces the functional and structural
changes in the urinary sphincter complex seen in women with
clinical SUI. In these studies, we modeled both acute and chronic
SUI in younger and older female NHPs with varying degrees of
estrogen deficiencies and impaired glucose/insulin metabolism.
With an n=6/experimental group, autologous skeletal muscle
precursor cells (skMPCs) were isolated from a muscle biopsy,
expanded to 5 million cells and injected directly into the urinary
sphincter complex of NHPs with SUI. skMPCs almost completely
restored sphincter muscle content and urethral pressures in
younger (5-8years) NHPs (p<0.05 vs. SUI/no treatment), but not
older (15-28 years) NHPs (p>0.05 vs. SUI). This same pattern
of efficacy was observed in NHPs with acute vs. chronic SUI,
in intact vs. ovariectomized NHPs; in normal cycling dominant
NHPs vs. dysmenorrheic subordinate NHPs and in normal
weight/normal glucosemetabolismvs. heavier impaired glucose/
insulin ratio NHPs. Thus, there are multiple determinants of cell
therapy efficacy that can be modeled in NHPs and are critical to
translational applicability of regenerative medicine approaches to
tissue repair.
kwilliam@wakehealth.eduDeterminates of cell therapy efficacy for tissue and organ
repair
Williams J K, Dean A, Lankford S
and
Andersson K E
Wake Forest Institute for Regenerative Medicine, USA
J Transm Dis Immun 2018, Volume 2
DOI: 10.21767/2471-8084-C1-003