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Title: Behavioral and histological analyses of human umbilical cord blood and embryonic stem
cells transplantation in a rodent model of Parkinson’s disease
Authors: L. P. KELLY 1 , *M. B. NEWMAN 1 , A. P. SMITH 2 , R. A. E. BAKAY 1 ;
1 Depts.NeuroSurg & Pharmacol, 2 Dept.NeuroSurg, Rush Univ. Med. Ctr., Chicago, IL
Abstract: We previously reported the first study indicating human umbilical cord blood (hUCB)
cells, both the heterogeneous mononuclear fraction (MNF) and neural-induced CD-133
(nCD133) stem cells (a subclass of hUCB cells), yield significant behavioral improvements over
neural-induced human embryonic stem cells (nhESC) in Parkinson’s Disease. In comparison to
hESCs, hUCBs are a heterogeneous population rich in haematopoietic stem and progenitor cells,
lack ethical implications, can be collected easily and noninvasively, are more immune immature
than other adult stem cells, and have over two decades of history in treating various
nonmalignant and malignant diseases.
We provide further immunohistological data on our study that determined the viability and
potential of nhESCs, MNF and nCD133s to repair, replace, or regenerate the loss of dopamine
(DA) in the striatum of Parkinsonian-like rats. Rats (n=28) were lesioned twice in the right
medial forebrain bundle with 6-hydroxydopamine (6-OHDA) or sham lesioned (n=8). Baseline
rotational behavioral testing was performed 1-2 days before lesion surgery and 3 weeks after for
inclusion criteria. In this model of PD, at least 60% of DA neurons in the SNpc are lost, with
~80% depletion of DA levels in the striatum, and full PD-like motor deficits are observed by 3
weeks post lesion. Unilateral cell transplantations were performed into the ipsilateral striatum
with either nhESCs, MNF, or nCD133s. In each group of rats, the brains, spleens, bone marrow
and peripheral blood were taken for immunohistochemical dependent measures. Tissue sections
were stained for tyrosine hydroxylase (TH), neuronal nuclei (NeuN), human nuclei (HuN), or
double-labeled for NeuN/HuN and TH/HuN for cell counts.
The specific aim of our study was to determine whether the nCD133 stem cells could yield
behavioral improvements that have been previously reported for nhESC transplantations. The
most fundamental finding was that both the MNF and nCD133s produced significant
improvements in the rotational, swing, and forelimb behavioral tests to nearly complete recovery
at 1 and 2 months. The nhESC stem cells, however, only showed significant improvements in the
swing and forelimb behavioral tests at 1 and 2 months. In addition, histologically, the
transplanted hUCB cells appeared to be more numerous and widely distributed than the nhESCs.
Interestingly, both hUCB groups were distributed bilaterally and heavily localized throughout
blood vessels. We are now determining whether the cells migrate outside the CNS.
Disclosures: L.P. Kelly, None; M.B. Newman, None; A.P. Smith, None; R.A.E. Bakay,
None.
Poster
532. Parkinson's Disease: Rat and Mice Toxins
Location: South Hall A