Bone Marrow Collection in Healthy Volunteers

Stem cells are able to replace damaged cells and to modulate inflammatory
processes and prevent dying of these cells. Traumatic Spinal cord injury is a
lifelong disabling disease and patients with a spinal cord injury needs
permanent nursing and support and their life expectancy is impaired. Patients
with a traumatic spinal cord injury are in general young and up to date no
treatment exists.
In literature it is mentioned that bone marrow derived stem cells are
pluripotent meaning that they can differentiate in all kind of cell-types and
thereby have the potential capability of replacing damaged cells.
Stem cells can divide in progenitor cells and can modulate inflammation by
producing factors which can stimulate of inhibit inflammation. Depending on the
environment, stem cells can also produce neurotrophic factors which can prevent
damaged cells from dying. The mechanism of these trophic factors is mainly
offering neuroprotection and preventing apoptosis.
The use of patients own bone marrow derived stem cells (autologous cells) have
the advantages that these cells are not rejected and are expected to be safe.
This research is focussed to determine the safety and to establish proof of
concept of human derived stem cells administered intrathecally into the
cerebrospinal fluid. Finally the samples are also used to characterize the
intended product extensively.
These activities are needed before formally a human experiments can be started.
These studies are needed for filing in the end for a human clinical trial.

The objective of this project is to collect fresh human bone marrow and to
process this bone marrow to an intended product in a short time to enable the
use of this product in the acute phase of a disease/disorder/lesion of the
central nervous system. the mode of action is supposed to offer protection to
damaged neurons and thereby decreasing the disability and to improve
neurological outcome.

This project is needed to prepare a human double blind randomized placebo
controlled clinical trial with the intended product in patients with a chronic
spinal cord injury.

This project needs the fresh bone marrow derived stem cells to establish the
following:
a. Install and adjust the manufacturing process and to define release criteria
b. to define the ranges and to characterize the content of the intended product
extensively
c. to establish proof of concept in an acute and in a chronic animal model with
a compression spinal cord injury
d. to perform the regulatory preclinical safety studies including
tumoigenicity, toxicity and biodistribution based on intrathecal
administration.

This project is no intervention. The purpose is to collect from healthy
volunteers bone marrow for processing and performing preclinical studies. The
intended product is not used in this phase to treat humans. The project
collects vital information to obtain approval for a clinical trial. Without
this no clinical trial can be applied.

A bone marrow collection for diagnostics and for treatment is a standard
accepted and safe procedure. The procedure itself is performed at one site of
the iliac crest under locally applied anesthetics. During the collection it is
possible to experience some temporary discomfort especially during the filling
of the first tube. After the collection, the volunteer may experience dolor at
the site of the puncture an this can persists for several hours. Sometimes this
discomfort is experienced during walking and bicycling. In rare occasions this
discomfort may last for several days and the use of pain medication is
indicated. In theory there is a small chance of contamination with skin
microbes. The use of skilled and trained physicians with the special defined
SOP prevents this as much as possible.