Fig. 1: Cell product survives and protects motor neurons and is safe in the spinal cord. | Nature Medicine

Fig. 1: Cell product survives and protects motor neurons and is safe in the spinal cord.

From: Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial

Fig. 1

a, Immunohistochemistry with human-specific nuclear marker SC121 (red) demonstrated dose–response engraftment of CNS10-NPC-GDNF, around host spinal cord ChAT-positive motor neurons (green). b,c, Human-specific GDNF antibody revealed a large region of staining post-transplantation of all cell doses (b), with quantification showing a clear dose-dependence at disease onset (c). d, Dose-dependent increase in motor neuron (MN) survival. e, A meningeal reaction occurred at disease onset in SOD1 and wild-type rats receiving all cell doses and vehicle, and was qualitatively larger at higher doses. f, Nissl stain of meningeal reaction at the surgical site in the region of the dorsal root entry, with qualitative score (0–4). Sample size n = 15 biologically independent animals for each dose and n = 10 for vehicle. g,h, Immunohistochemistry with human-specific GDNF antibody showed immunodeficient rats had GDNF production at multiple transplant sites for up to 180 d (g), with GDNF uptake by host motor neurons (h). i, H&E stain showed a meningeal reaction associated with the DREZ near the cannula insertion site. j–l, Immunohistochemistry showed that these structures occasionally had (j) the cellular product within them based on a human-specific marker for nestin, (k) were positive for Schwann-like cells based on S100b and (l) contained numerous small-diameter axons based on a neurofilament heavy stain. Sample size n = 12 and n = 40 biologically independent animals for 30- and 180-d timepoints, respectively. Scale bars, 75 µm (a); 500 µm (b,f,i,j); 100 µm (h); 20 µm (k,l). A general linear regression model was used for ELISA (c) and was Tukey-adjusted for multiple comparisons. *MFD versus vehicle and MFD versus dose 1, P < 0.0001; #MFD versus dose 2, P = 0.0027; ^MFD versus dose 3 P = 0.0009. A mixed-model regression with compound symmetry covariance structure was used for the motor neuron counts (d) and Tukey-adjusted for multiple comparisons. *MFD versus vehicle and MFD versus untreated conditions, P < 0.0001; #MFD versus dose 1 P = 0.01387; ^MFD versus dose 2, P = 0.02299. Differences were considered significant at the two-sided level of P < 0.05. Error bars, ±s.e.m.

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