Jade Clawson

Evelyn Galvez
Biology 1615
July 2, 2018
Defining the Optimal Window for Cranial Transplantation of

Human Induced Pluripotent Stem Cell-Derived Cells to

Ameliorate Radiation-Induced Cognitive Impairment

Introduction

Chemotherapy and radiotherapy (radiation) are destructive methods used to destroy the

fastest growing cells in the human body. Cancerous cells multiply rapidly which is why

these methods are used when treating those with cancer. However, the human body

has many different types of cells which also multiply at astonishing rates. Therefore,

chemotherapy and radiotherapy do not just destroy cancerous cells; these treatments

destroy hair cells, bone marrow, cells within the brain like progenitor cells, neural cells,

microglial cells, etc. Chemotherapy and radiotherapy also inhibit neurogenesis

(creation of new neurons), cause or increase neural inflammation, and compromise the

structure of the neurons in the brain which can have devastating effects. Munjal M.

Acharya, Vahan Martirosian, Lori-Ann Christie, Lara Riparip, Jan Strnadel, Vipan K.

Parihar, and Charles L. Limoli are a group of scientists that conducted an experiment on

rats to test the cognitive effects of human neural stem cells (hNSCs) in patients who

have received chemotherapy and radiotherapy. The overall goal for these scientists is to

find the best possible time to graft human neural stem cells into the hippocampus of the

brain following irradiation to decrease cognitive dysfunction caused by chemotherapy

and radiotherapy in order to maximize positive results.

Materials and Methods

In this experiment, 44 male 2-month old rats were separated into 5 different groups.

Group 1 received no irradiation with sham-surgery controls. Group 2 was irradiated but

had sham-surgery controls. Groups 3-5 were irradiated and engrafted with hNSCs at

different times. Group 3 was engrafted 2 days after irradiation, Group 4 was engrafted 2

weeks after irradiation, and Group 5 was engrafted 4 weeks after irradiation. The rats

that were irradiated and engrafted with hNSCs (groups 3-5) were tested 1 month after

the transplantation of the stem cells. These rats underwent novel place recognition

(NPR) testing that assessed spatial recognition memory and contextual fear-

conditioning in the hippocampus. Once cognitive testing had been completed, the rats

were sacrificed, and their brains were processed for coronal sectioning. The brains were

then stained and examined in order to identify possible newly activated microglia.

Results

Results of this experiment showed that the rats that received hNSCs had definite

improvement in hippocampal spatial memory, contextual fear-conditioning, and

performance when compared to the rats that had sham-surgery controls and did not

receive grafted human stem cells. Within Groups 3-5, Group 5 showed superior

performance. This is evidence that postponing surgery to engraft hNSCs 4 weeks after

irradiation will result in the most positive outcome in improving cognitive dysfunction.

Within the brains of the Group 5 subjects, significant analysis presented differentiation

of the majority of grafted neural stem cells into multiple immature and even mature

neuronal, astrocytic, and oligodendroglial cells within the irradiated hippocampus.

Discussion

Chemotherapy and radiotherapy disrupt overall hippocampal function by inhibiting

neurogenesis and increasing neural inflammation. These experimental findings have

created a possible relief for cancer survivors through stem cell therapy and may

improve quality of life for many individuals suffering from any of the inadvertent side-

effects of chemotherapy and radiation.

References

Defining the Optimal Window for Cranial Transplantation of Human Induced Pluripotent
Stem Cell-Derived Cells to Ameliorate Radiation-Induced Cognitive Impairment.
Munjal M. Acharya, Vahan Martirosian, Lori-Ann Christie, Lara Riparip, Jan Strnadel,
Vipan K. Parihar, and Charles L. Limoli