Figure 1.
Transplanted iPSC improved functional recovery by Morris water maze testing.
(A) The swim tracks of the rats during Morris water maze testing. The QA+iPSC rat obviously spent less time searching for the platform than the QA+PBS rat. (B) Comparison of the latency to find the platform among the three groups in Morris water maze testing. (C) Comparison of the crossovers among the three groups in probe test of Morris water maze testing. The 3 groups are presented as control (saline injection), QA+PBS (QA injection with PBS transplantation); and QA+iPSC (QA injection with iPSC transplantation) groups. Error bars represent SD, and * P<0.05, compared between control and QA+PBS groups; ★ P<0.05, compared between control and QA+iPSC groups; # P<0.05, compared between QA+PBS and QA+iPSC groups.
Figure 2.
Enhanced glucose metabolism and decreased striatal atrophy following iPSC transplantation.
(A) Serial PET images demonstrating metabolism recovery after stem cell treatment for QA-treated rats. Images are shown in axial view. Scale was set according to signal intensity. (B) Semiquantitative analysis of variance of glucose metabolism after stem cell transplantation in each group. (C) Photomicrographs show the difference in striatal volumes in unilateral lesion rat. There was no striatal atrophy in the control group, but the striatal volumes in the lesion side of QA+PBS and QA+iPSC groups were significantly decreased compared with the contralateral side. Arrow indicates surgery sites in each group. (D) Quantification of striatal volumes show increased volumes in the QA+iPSC group. The 3 groups are presented as control (saline injection), QA+PBS (QA injection with PBS transplantation); and QA+iPSC (QA injection with iPSC transplantation) groups. Error bars represent SD, and * P<0.05, compared between control and QA+PBS groups; ★ P<0.05, compared between control and QA+iPSC groups; # P<0.05, compared between QA+PBS and QA+iPSC groups.
Figure 3.
Neuronal loss and gliosis in striatum induced by QA injection.
(A, C, E, G and A', C', E', G') Immunohistochemical staining for NeuN (A–A'), Darpp32 (B–B'), GFAP (C–C'), Iba-1 (D–D') in striatum in the control rats. (B, D, F, H and B', D', F', H') Immunohistochemical staining for NeuN (B–B'), Darpp32 (D–D'), GFAP (F–F'), Iba-1 (H–H') in striatum in the QA-treated rats, which showed the loss of NeuN- and Darpp32-positive neurons and proliferations of astrocyte and microglia in the lesion area. A–H were the same magnification; A'–H' were the same magnification; A'–H' were the higher magnification views of the red box in A–H. (I) Comparison of the number of NeuN- and Darpp32-positive neurons in striatum among the three groups. (J) Comparison of the optical density of GFAP- and Iba-1-positive glial cells in striatum among the three groups. The 3 groups are presented as control (saline injection), QA+PBS (QA injection with PBS transplantation); and QA+iPSC (QA injection with iPSC transplantation) groups. Error bars represent SD, and * P<0.05, compared between control and QA+PBS groups; ★ P<0.05, compared between control and QA+iPSC groups; # P<0.05, compared between QA+PBS and QA+iPSC groups.
Figure 4.
Transplanted iPSC migrated into the lesioned striatum after QA injection.
(A, B) Nissl staining of striatum after iPSC transplantation. B was the higher magnification views of the black box in A. (C) Migration and distribution of the transplanted iPSC in QA-lesioned striatum were observed under fluorescence microscope. B and C were the same magnification.
Figure 5.
Transplanted cells differentiate into neurons and astrocytes in lesioned striatum.
Transplanted iPSCs show green fluorescence; immunostaining with antibodies against NeuN (A), Darpp32 (B), GFAP (C) and Iba-1 (D) show red fluorescence; nuclei stained with Hoechst 33258 show blue fluorescence; and merged images show that engrafted iPSC express neuron, projection neuron, astrocyte, or microglia features.
Figure 6.
Increased protein expression of neurons and glia cell in striatum after iPSC transplantation.
(B) was the semiquantitative analysis of (A) expressed as relative optical density, which showed that the levels of NeuN, Darpp32, GFAP and Iba-1 proteins increased after iPSC transplantation. The 3 groups are presented as control (saline injection), QA+PBS (QA injection with PBS transplantation); and QA+iPSC (QA injection with iPSC transplantation) groups. Error bars represent SD, and *P<0.05, compared between control and QA+PBS groups; ★ P<0.05, compared between control and QA+iPSC groups; # P<0.05, compared between QA+PBS and QA+iPSC groups.