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. 2006 Aug 23;1106(1):46-51.
doi: 10.1016/j.brainres.2006.05.109. Epub 2006 Jul 10.

Adult human bone marrow stromal spheres express neuronal traits in vitro and in a rat model of Parkinson's disease

Sokreine Suon  1 , Ming Yang  2 , Lorraine Iacovitti  3
Affiliations

Adult human bone marrow stromal spheres express neuronal traits in vitro and in a rat model of Parkinson's disease

Sokreine Suon et al. Brain Res. .

Abstract

Adult human bone marrow stromal cells (hMSCs) grown in suspension culture gave rise to spheres of neural progenitor (NP) cells, capable of expressing both dopaminergic (DA) and GABAergic (GABA) traits. After transplantation into the Parkinsonian rat, human NPs and neurons were present at 2 weeks. Although no DA neurons appeared to survive transplantation, there were abundant GABA neurons present in the graft. By 4 weeks, however, all cells had died. Finding ways to prolong survival and promote the appropriate neurotransmitter phenotype is essential if hMSCs are to be clinically useful.

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Figures

Fig. 1
Fig. 1
Generation of DA neurons from adult hMSC spheres. Cells from the hMPC 32F line were propagated in a protocol similar to the cultivation of neural progenitor cells. HMPC 32F were mechanically dissociated and cultured in suspension in a serum-free growth medium containing epidermal growth factor and basic fibroblast growth factor. Spheres were further differentiated by treating them in serum-free medium containing a differentiation cocktail (200 nM TPA + 250 μM IBMX + 50 μM Forskolin) for 3 h and dibutyryl cAMP for 7 days.
Fig. 2
Fig. 2
Characterization of cells in human MSC spheres. Immunocytochemical localization of Oct-4 (A), nestin (B;I), β-tubulin III (C; J), Fn (F), SSEA4 (G), Sox-2 (H), NF (K), Pitx-3 (L), TH (D, M, N), DA (N), and GABA (E, O) in DA-hMSC spheres (A–E) or in cells which migrated away from adherent DA-hMSC spheres (F–O). All stained cultures were mounted in Prolong Gold for nuclear staining with DAPI (Invitrogen). High power (40×) insets are included in panels F–O.
Fig. 3
Fig. 3
RT-PCR analysis indicated that NP-hMSC spheres expressed neuronal markers (nestin, Nurr-1, and β-tubulin III). In contrast, only DA-hMSC spheres expressed specific midbrain DA markers (Pitx-3, AADC, GIRK2, and TH).
Fig. 4
Fig. 4
Characterization of NP-hMSC spheres 1 week after transplantation into the striatum of 6-OHDA-treated rats. Immunocytochemical localization of hunu (A), nestin (B), and images merged in panel C, β-III tub (D), TH (E), and images merged in panel F, hunu (G, GABA (H) and images merged (I)). High-power (40×) insets are included in panels A–D, F, G–I.
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