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2 years postinfusion data for the entire23-subject cohort of
umbilical cord bloodrecipients will be important in more
con-clusively documenting the efficacy of au-tologous umbilical
cord blood infusion intype 1 diabetes.
Because neither the FDA nor our localinstitutional review board
would allow
for a randomized or blinded study, wewere unable to perform
age-matchedcomparisons of meal-stimulated endoge-nous insulin
production. Furthermore,the lack of comparative
meal-stimulatedC-peptide data in young children withtype 1 diabetes
made historical compari-sons impossible. Comparison to an
age-matched group of type 1 diabetic patientsdemonstrated that
subjects receiving um-bilical cord blood infusion maintained A1Cand
insulin requirements below what mostclinicians would expect in such
young chil-
dren. Nevertheless, among umbilical cordblood recipients, peak
and area underthe curve C-peptide levels 1 year postumbilical cord
blood infusion declined sig-nificantly when compared with
baselineand fractional changes in A1C, and insulinrequirement were
no different when com-paring umbilical cord blood recipients
andhistorical control subjects.
As we further explore potential appli-cations of autologous
umbilical cordblood in treating type 1 diabetes,
practicalconsiderations will continue to drive ourapproach.
Notably, the cell counts recov-
ered from privately banked cord bloodunits used in our study
were routinely anorder of magnitude lower than cell countsfrom
publicly banked units prepared us-ing the same techniques. This
should notnecessarily impugn private cord bloodbanks for providing
substandard storagebut more likely reflects the frequency oflow
cell counts at collection and explainswhy publicbanks collect
andthen discarda large percentage of donated units. Therelatively
low cell counts used in thisphase I study may indicate that
much
higher cell counts are needed to inducerelevant immunologic or
metabolic ef-fects. Additional efforts to improve collec-tion,
storage (i.e., multiple aliquots), cellrecovery, and expansion of
umbilical cordblood are urgently needed to allow for thedevelopment
of additional applicationsbeyond traditional umbilical cord
bloodtransplantation.
Additionally, the dictum of primumnon nocere must remain
paramountwhen discussing interventional therapiesfor young children
with type 1 diabetes.The development of both safe and effec-
tive therapies to preserve -cell functionin patients with type 1
diabetes presents aformidable catch-22. Although high-potency
immunosuppressive and immu-nomodulatory cocktails may indeed beable
to preserve C-peptide levels in re-cently diagnosed patients (14),
such ap-proaches are associated with considerablerisk of morbidity
and even mortality.Type 1 diabetes is inarguably a diseasewith
substantial short-term and long-term complications. Nevertheless,
insulinis fairly effective, albeit a cumbersomeand imperfect
therapy. Our group haslong espoused the need to use combina-tion
approaches much like those that haveproven effective in treating
cancer or HIV(25). Still, we must recall that type 1 dia-betes is
neither cancer nor HIV. Potentialcombination approaches, including
thosethat include cell therapy, should be asso-ciated with
appropriately low risk pro-files, especially when being
consideredfor use in children.
The potential of umbilical cord bloodto participate in the
future of type 1 dia-betes interventional therapies exists.
Nev-ertheless, multiple therapeutic avenueswill need to be
explored, and several mo-dalities will likely need to be combined
toachieve the dream of safely and perma-nently reversing or
preventing type 1 di-abetes. Future efforts to use autologous
umbilical cord blood in the treatment oftype 1 diabetes will
continue with empha-sis on mechanistic studies, establishmentof
age-appropriate comparative groups,and addition of multiple safe
therapies(i.e., vitamin D and n-3 fatty acids) inhopes of achieving
synergy.
Acknowledgments This study was fundedby Juvenile Diabetes
Research Foundation(JDRF) Innovative Grant 1-2005-362, JDRFCenter
Grant 4-2007-1065, National Insti-
tutes of Health (NIH) Contract M01RR00082,and NIH Grant
1R21DK07758001.
No potential conflicts of interest relevant tothis article were
reported.
The sponsors of the study had no role in thestudy design, data
collection, data analysis,in-terpretation of data, or writing of
the report.
We acknowledge the assistance of Hilla-LeeViener (laboratory
technician), Douglas Theri-aque (data manager), the stem cell
laboratorystaff and nurses, the General Clinical ResearchCenter
staff and nurses, and, most impor-tantly, the children and families
who partici-pated in this phase I trial.
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