Endometrial stem cell transplantation in MPTP- exposed primates: an alternative cell source for treatment of Parkinson's disease

Abstract

Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. Cell-replacement therapies have emerged as a promising strategy to slow down or replace neuronal loss. Compared to other stem cell types, endometrium-derived stem cells (EDSCs) are an attractive source of stem cells for cellular therapies because of their ease of collection and vast differentiation potential. Here we demonstrate that endometrium-derived stem cells may be transplanted into an MPTP exposed monkey model of PD. After injection into the striatum, endometrium-derived stem cells engrafted, exhibited neuron-like morphology, expressed tyrosine hydroxylase (TH) and increased the numbers of TH positive cells on the transplanted side and dopamine metabolite concentrations in vivo. Our results suggest that endometrium-derived stem cells may provide a therapeutic benefit in the primate model of PD and may be used in stem cell based therapies.

Keywords: MPTP; Parkinson disease; adult stem cells; endometrium; mesenchymal stem cells; neurodegenerative diseases; stem cells; transplantation.

Fig. 1

MPTP treatment resulted in a significantly lower HVA concentration in the recipient animals compared to the untreated animals (P < 0.05, t-test). Striatal HVA concentrations were measured in untreated monkeys and the sham-injected side of the MPTP-treated animals (MPTP)

Fig. 2

Schematic illustration of engraftment and migration of EDSCs. After stereotaxic injection, endometrium-derived stem cells (EDSCs) engrafted into the striatum and migrated to the substantia nigra, where some of the EDSCs exhibited neuron-like morphology and expressed tyrosine hydroxylase (TH).

Fig. 3

Tyrosine hydroxylase-expressing neuron-like cells derived from endometrial stem cells. Immunofluorescence analysis of PKH26-labelled EDSCs. Some of the PKH26- labelled EDSCs (red) exhibited neurite-like projections and expressed tyrosine hydroxylase (green) 4 weeks after intrastriatal injection (400×).

Fig. 4

Striatal HVA Concentrations in MPTP-treated monkeys (ng/dl). (A) EDSC injection was associated with higher striatal HVA concentration compared with the sham injection. (B) Striatal HVA concentrations increased 12.5 ng/mg in Monkey #1, 5 ng/mg in Monkey #2 and 7.5 ng/mg in Monkey #3, with a mean increase of 8.2 ng/mg protein (P < 0.05, t-test) The average change of striatal HVA concentration corresponds to a mean of 27.7% increase on the EDSC-injected side compared to the sham-injected side of the MPTP-treated monkeys (abbreviations: Sham: Sham-injected side of the MPTP-treated monkeys; EDSC: Endometrium-derived stem cell injected side of the MPTP-treated monkeys).