A Lab on a Chip to Isolate Human Skeletal
Stem Cells for Bone Regeneration
J.M. Xavier1,2,*, P. Rosendahl3, D. Spencer1, O. Otto3, J. Guck3, R.O.C. Oreffo2, H. Morgan1
School of Electronics and Computer Science, University of Southampton, Southampton, UK.
2 Centre for Human Development, Stem Cells and Regenera-tion, Institute of Developmental Sciences, Southampton General Hospital, Southampton, UK.
3 Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
* [email protected]
1
Motivation and Introduction
1. Stem cells are cells with infinite
growth and differentiation capacity.
The most powerful stem cell known
is the fertilised egg which gives rise
to a whole new human being and is
called a Totipotent Stem Cell.
2. Pluripotent Stem Cells are
found in embryos. However,
their use is limited by ethical
and religious considerations.
3. Stem cells exist even in adults. They are
responsible for replacing old cells in our
bodies and are called Multipotent Stem
Cells. These are advantageous as we can
use a person’s own cells to treat them.
4. In the bone marrow we can find
haematopoietic stem cells that renew our
immune system. We also find Skeletal Stem
Cells which have the capacity to regenerate
bone and cartilage.
5. These cells are extremely rare, as
few as 1 in every 100,000 cells in
the human bone marrow.
6. Microfluidics provides new
methods for isolating these
cells based on differences in
their size and deformation.
7. Skeletal stem cells could be isolated
with high purity and efficiency and in a
sufficient number for clinical application.
8. These cells can be grown to promote bone
regeneration in patients with bone trauma
or disease such as: fractures, osteoporosis or
osteoarthritis.
Single Cell Characterisation
Skeletal Stem Cells are larger and stiffer than other cells in the bone marrow
Human Bone Marrow
Real-Time Deformability Cytometry
Lymphocyte
Lymphocyte
Granulocyte
Skeletal Stem
Cell
Cell Separation
Deterministic Lateral Displacement is a microfluidic sorting technique sensitive to differences in
cell size and deformation
The larger and less deformable Skeletal
Stem Cells are collected in one reservoir
Size based separation
Deformability based separation
All the remaining cells in the bone marrow
are collected in a different reservoir
2 cm
ACKNOWLEDGEMENTS
This work was supported by the European Commission through the Label-free particle sorting (LAPASO) project from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/20072013/ under REA grant agreement n° 607350.
The authors would like to acknowledge Sarah Helps for fabricating the microfluidic impedance chips. Acknowledgements are also due Claudia Moex for all the collaboration with the cell work at the Biotechnology Center in Dresden.
The authors would also like to express their gratitude to the surgeons from Southampton General Hospital and the Spire Southampton Hospital for providing the patient bone marrow samples.
www.soton.ac.uk