Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury

Stem Cell Res, 2015 · DOI: 10.1016/j.scr.2015.07.001 · Published: September 1, 2015

Spinal Cord Injury Neurology Regenerative Medicine & Stem Cells

Simple Explanation

This study investigates how different doses of transplanted human neural stem cells (hCNS-SCns) affect their survival, growth, and movement within the injured spinal cord of mice. The research found that higher doses of stem cells didn't necessarily lead to better engraftment, suggesting the spinal cord's capacity to support these cells has limits. The study also observed that lower doses of stem cells tended to proliferate more, indicating that the host environment might regulate cell growth based on cell density.

Study Duration

16 Weeks

Participants

Immunodeficient NOD-scid mice

Evidence Level

Not specified

Key Findings

1
Transplant dose was inversely correlated with measures of donor cell proliferation at 2 weeks post-transplant (WPT) and dose-normalized engraftment at 16 WPT.
2
Mice receiving the highest cell dose exhibited an engraftment plateau, in which the total number of engrafted human cells never exceeded the initial dose.
3
Increasing transplantation dose increased the number of donor cells localized in the caudal niche at 16 WPT.

Research Summary

The study quantitatively evaluated the effect of transplantation dose on the spatiotemporal dynamics of human neural stem cell engraftment in the injured central nervous system. The findings suggest that the spinal cord injury (SCI) niche has a limited capacity to accommodate/integrate donor cells, leading to an engraftment plateau at higher doses. Donor cell expansion was inversely regulated by target niche parameters and/or the initial donor cell density.

Practical Implications

Optimizing Cell Therapies

Understanding the dynamics of donor cell engraftment, proliferation, and migration is important for optimizing cell therapies for the injured or diseased CNS.

Defining Target Cell Dose

The response of transplanted cells to the host microenvironment should be a key variable in defining target dosing in pre-clinical models of CNS disease and injury.

Enhancing Donor Cell Engraftment

Inclusion of a transplantation matrix or exogenous growth factors might enhance donor cell engraftment after epicenter transplantation.

Study Limitations

1
The study was conducted in immunodeficient mice, which may not fully represent the human immune response.
2
Only a small proportion of cells (9–29%) survived the transplantation process.
3
The long-term effects of transplantation dose on functional recovery were not directly assessed.

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