New Therapies for bone and cartilage defects using bone marrow

Large cartilage defects or large bone defects can occur due to trauma or
surgical resection of a tumor. They do not heal spontaneously and need
intervention. Since bone marrow contains cells with capacity to differentiate
into cartilage or bone (1-3), it is a potentially suitable source for cells
for generation of new cartilage and bone to repair defects. Before these cells
can be used to treat patients we need to be able to make sufficient amount of
good quality tissue. The last decade research of us and others have
contributed to improved cartilage and bone formation by these cells (4-9). But
for application we need more knowledge on what influences differentiation of
the cells and formation of cartilage or bone tissue to be able to improve the
quality and the reproducibility of the tissue formed for each patient in
future.

Besides having the capacity to differentiate into different types of cells,
such as cartilage and bone cells, these cells from the bone marrow have
recently been shown to be able to influence their environment by the secretion
of factors (10). The secreted factors can inhibit inflammation, or stimulate
tissue regeneration or angiogenesis. This way they can play an important role
in disease modification as well as tissue repair. We have recently demonstrated
that the factors secreted by these cells can indeed inhibit disease processes
in osteoarthritic joint tissues in vitro (11) as well as have effects on pain
when injected in an osteoarthritic rat joint (12) . MSC are being applied in
experimental clinical studies to repair cartilage defects or osteoarthritis
(13,14). How these cells do this and how they should be treated to use this
property in the treatment of disease is largely unknown at the moment.

The aim of the basic research in the laboratory is to develop new treatments to
repair large bone defects, repair cartilage defects or inhibit the progression
of osteoarthritis (cartilage degeneration).
We focus on the following questions:
1.How can we obtain cartilage from bone marrow derived cells that is of
sufficient quality to repair cartilage defects?
We will amongst others use various growth factors, biomaterials and culture
procedures. The cells will be used in in vitro experiment and where appropriate
in animal experiments (after approval by animal ethical committee)
2.How can we use bone marrow derived cells to repair bone defects?
We will amongst others use various growth factors, biomaterials and culture
procedures. The cells will be used in in vitro experiment and where appropriate
in animal experiments (after approval by animal ethical committee).
3.Can bone marrow derived cells been used to inhibit the progression of
osteoarthritis? How can we apply the cell? What is the mechanism of action?
We will use several in vitro models with osteoarthritic tissues (obtained with
approval of medical ethical committee) as well as in vivo experiments in mice
and rat (with approval of animal ethical committee)


With the remaining bone marrow we will investigate the presence of immune cells
in the bone marrow. From mice it is known that immune cells including T- helper
memory cells are present in the bone marrow (15). Unpublished observation from
our group shows the presence of Th2 cells, the T-cell responsible for allergic
inflammation, in the bone marrow of house dust mite asthmatic mice. The
detection of and the presence of cytokine producing and chemokine receptor
expressing T-cells in the bone marrow suggest that skewing of immune cells
occurs already in the bone marrow. Next we want to know how and if these immune
cells influence the microenvironment of stromal cells and if and how these
structural cells instruct precursors for other immune cells.

Bone marrow samples will be collected and transported to the lab. The person on
duty in the lab will follow the standard operating procedures to get the
mesenchymal stromal cells in culture. The cells will then be used in
experiments aimed on development of better treatments for bone and cartilage
diseases. If marrow aspirate is received than required for the experiments
the marrow might might be used in the department of pulmonary. The immune cells
will be isolated from the biopsy and used for experiments to study the presence
and function of immune cells in the bone marrow.

not applicable

There is no risk for the participants. We have done this procedure in almost
200 patients without any adverse event of any kind. There is no burden to the
patients since the biopsy will be taken during the hip replacement surgery when
the patient is under anesthesia. The research that becomes possible by the
availability of the bone marrow can contribute to the development and
improvement of future therapies.