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Brain & Heart Human DPSCs attenuated amyotrophic lateral sclerosis in mice

with that in vehicle-treated SOD1-G93A mice from the 3.4. hDPSCs infusion exerted no obvious effect on
13 week onward (Figure 1D, 18 week p = 0.0008). Finally, glial cell phenotypes in SOD1-G93A mice
th
th
the infusion of hDPSCs prolonged the survival of SOD1- Previous research has shown that microglial activation
G93A mice by approximately 15 days (169.7 ± 1.997 vs. can exacerbate cellular damage in ALS development.
22
154.3 ± 3.803 days; p = 0.0037, Figure 1E and F). To further investigate the effect of hDPSCs infusion on
3.2. hDPSCs infusion reduced the degree of spinal microglia in ALS mice, we performed immunofluorescence
cord atrophy in SOD1-G93A mice staining and flow cytometry. Immunofluorescence staining
revealed an increased number of microglia in the spinal
Cross-sectional images of lumbar enlargement (LE) were cords of all SOD1-G93A mice on day 150 (Figure 4A and B;
acquired by 7-T MRI. Comparatively, the average area of p < 0.0001). The number of microglia in the spinal cord
LE in T2WI scans was reduced in all SOD1-G93A mice and brain of SOD1-G93A mice was significantly higher
on days 120 and 150 (Figure 2A and C). On day 120, than that of WT mice (Figure 4D and E; p = 0.0005 for
the average area of LE was smaller in vehicle-treated the brain, p < 0.0001 for the spinal cord), suggesting that
SOD1-G93A mice than in WT mice (2.999 ± 0.031 vs. microglia are involved in the disease progression of ALS
3.280 ± 0.044 mm ; Figure 2B; p = 0.0004). The average mice. However, a significant difference was detected in
2
area of LE in hDPSC-treated SOD1-G93A mice was the number of microglia between the hDPSCs-infused
greater than that in untreated mice (3.149 ± 0.033 vs. and vehicle groups (Figure 4B, D, E; p = 0.1433 for the
2.999 ± 0.031 mm ; Figure 2B; p = 0.0053). On day 150, brain, p = 0.1581 for the spinal cord), suggesting a limited
2
the average area of LE was smaller in vehicle-treated effect of hDPSCs on microglia in ALS mice. Furthermore,
SOD1-G93A mice than in WT mice (2.733 ± 0.031 vs. no significant differences were observed in the number
3.451 ± 0.066 mm ; Figure 2D; p < 0.0001). The hDPSCs of astrocytes between the hDPSCs-infused and vehicle
2
infusion preserved the average area of LE in SOD1-G93A groups (p = 0.0937, Figure S3).
mice compared with that in vehicle-treated SOD1-G93A
mice (2.927 ± 0.027 vs. 2.733 ± 0.031 mm ; Figure 2D; 4. Discussion
2
p = 0.0008). Hence, treatment with hDPSCs could delay This study examined the efficacy of hDPSCs infusion in
spinal cord atrophy in SOD1-G93A mice. a mouse model of ALS. Our findings indicated that the
3.3. hDPSCs infusion preserved neurons in infusion of hDPSCs not only mitigated motor neuron
SOD1-G93A mice dysfunction but also extended the lifespan of SOD1-G93A
mice. Moreover, immunofluorescence and flow cytometry
The pathological features of hDPSCs infusion in the revealed that hDPSCs infusion could reduce the degree
ALS mouse model were characterized using flow of spinal cord atrophy and relatively preserve neurons in
cytometry and immunofluorescence. The results of SOD1-G93A mice.
immunofluorescence indicated a significant reduction in
the number of neurons in the spinal cord of SOD1-G93A MSCs, as pluripotent stem cells, are used to treat a variety
mice at 150 days (Figure 3A and B; p = 0.0001). of diseases, including ALS. 23,24 Compared with other MSCs,
Conversely, hDPSCs-treated SOD1-G93A mice exhibited hDPSCs have the characteristics of simple acquisition and
preservation of spinal cord neuron numbers compared easy expansion 25,26 ; however, their therapeutic effects in
with vehicle-treated SOD1-G93A mice (Figure 3A and B; ALS have not yet been reported. In the present study, the
p = 0.0030). Consistent with these immunofluorescence infusion of hDPSCs could significantly ameliorate clinical
findings, a remarkable decrease in the number of neurons disability and prolong survival time in ALS mice. This
was observed in the brains and spinal cord of SOD1-G93A effect was evidenced by 7-T MRI analysis, which showed
mice (Figure 3D and E; p = 0.0005 for brain, p = 0.0019 that the extent of spinal cord atrophy in hDPSCs-treated
for the spinal cord). After the infusion of hDPSCs, the mice was significantly less than that in untreated mice.
SOD1-G93A mice presented with an increase in the To further explore the cellular changes brought about
percentage of neurons in their brains and spinal cords by hDPSCs infusion, we performed flow cytometry and
(Figure 3D and E; p = 0.0076 for the brain, p = 0.0063 immunofluorescence staining to analyze neurons. The
for the spinal cord). Moreover, the number of BDNF- results were consistent with those of previous studies that
positive cells remarkably increased in SOD1-G93A mice used MSCs for ALS treatment, indicating that the number
after treatment with hDPSCs (Figure S2). These data of neurons was relatively preserved after the infusion of
27,28
suggest that hDPSCs have the potential to protect against hDPSCs.
neuronal loss and improve the secretion of neurotrophic Studies have shown that transplanted MSCs can
factors in an ALS mouse model. differentiate into motor neuron-like cells, expressing

Volume 2 Issue 4 (2024) 5 doi: 10.36922/bh.3996