Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus After Intrathecal Treatment with Adipose-Derived Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSC) have emerged as a new therapeutic tool for a number of clinical applications, because they have multipotency and paracrine effects via various factors. In the present study, we investigated the effects of adipose-derived MSC (Ad-MSC) transplantation via intrathecal injection through the cisterna magna on cell proliferation and differentiation of endogenous stem cells in the hippocampal dentate gyrus (DG) using Ki-67 (a marker for proliferating cells), and doublecortin (DCX, a marker for neuroblasts). The transplanted Ad-MSC were detected in the meninges, not in the hippocampal parenchyma. However, the number of Ki-67-immunoreactive cells was significantly increased by 83% in the DG 2 days after single Ad-MSC injection, and by 67% at 23 days after repeated Ad-MSC treatment compared with that in the vehicle-treated group after Ad-MSC transplantation. On the other hand, the number of DCX-immunoreactive cells in the DG was not changed at 2 days after single Ad-MSC injection; however, it was significantly increased by 62% 9 days after single Ad-MSC injection. At 23 days after repeated Ad-MSC application, the number of DCX-immunoreactive cells was much more increased (223% of the vehicle-treated group). At this time point, DCX protein levels were also significantly increased compared with those in the vehicle-treated group. These results suggest that the intrathecal injection of Ad-MSC could enhance endogenous cell proliferation, and the repeated Ad-MSC injection could be more efficient for an enhancement of endogenous cell proliferation and differentiation in the brain.

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

“…administration. Neurogenesis was reported previously by other authors following intrathecal and intraparenchymal administration of MSCs9192. On the contrary, CD31 plus Ki-67 did not show an increase in angiogenesis in treated animals compared to the control 14 days following cerebral ischemia.…”

Neuroprotective effects of adipose-derived stem cells against ischemic neuronal damage in the rabbit spinal cord

“…Images of CM-DiI labeled ASCs were confirmed through an inverted fluorescence microscope (IX 71, Olympus, Japan) equipped with a digital camera (DP71, Olympus) as previously described [22].…”

“…The same volume of vehicle (PBS) was injected in the same way of ASCs treatment. The technique of intrathecal injection was used by previously reported [22,24]. There were no obvious behavioral sequelae (e.g.…”

Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)

“…The “Beijing Declaration of IANR” (agreed upon at the IANR 2015 Conference in Tehran) declared as its fundamental tenet that “functional recovery is possible after central nervous system (CNS) injury and neurodegeneration” and noted that “cell therapies may become a key clinical therapeutic option for acute, subacute and/or chronic CNS diseases or damage” 5 . More than 30 types of cells have been identified through preclinical studies as having the capacity for neurorestoration 6 – 66 .…”