World’s first novel method for label-free identification of stem cells that will lead to more consistent and efficacious stem cell therapies


Left Pix: (L-R) Associate Professor Jerry Chan, SMART co-Investigator; Dr Zhiyong Poon, SMART Research Scientist and
Dr Jacky Lee, former SMART Postdoctoral Associate, with the microfluidics cell sorting device that isolates Mesenchymal
Stem Cells (MSCs) for bone and muscle therapeutic applications. This device can reduce the analysis and decision-making
process from 1 - 2 months to less than 3 days. Right Pix: Close-up of the microfluidics cell sorting device


New technique that identifies rare stem cells from bone marrow will give clinicians a fillip in stem-cell
treatment of joint, bone and muscle repair

A team of scientists and engineers at the Singapore-MIT Alliance for Research and Technology (SMART)
[新加坡-麻省理工学院科研中心] have invented a new technique to identify populations of rare stem cells from bone marrow
based on their different combinations of biophysical characteristics such as cell size, cell stiffness and nucleus deformation.

Mesenchymal stem cells (MSCs), a type of cells which resides in the bone marrow, can differentiate into cells that produce bone,
cartilage, fat or muscles – a trait that clinicians exploit for tissue repair. (See Factsheet below)

With better identification of MSCs, doctors can be certain that the concentration of highly enriched MSC mixture is as stated,
making it easier for them to develop stem-cell-based treatment that would be more consistent and produce better results.

Currently, there is no good way to separate MSCs from bone marrow cells that have already begun to differentiate into other
cell types, but share the same molecules on the cell surface. This may be one reason why research results vary among
laboratories and why stem-cell treatments now in clinical trials are not as effective as they could be, explained
Krystyn Van Vliet, Lead Investigator, SMART BioSystems and Micromechanics (BioSyM) Interdisciplinary Research Group (IRG).      

The research entitled ‘Multivariate biophysical markers predictive of mesenchymal stromal cell multipotency’ will be published
in the prestigious scientific journal Proceedings of the National Academy of Sciences this week. Lead authors of the paper
are Dr Jacky Lee and Dr Hui Shi, a former SMART Postdoctoral Associate.

Dr Jacky Lee [李旺城] carried out this work over five years as a graduate student and later as a Postdoctoral Associate in SMART
BioSyM under the supervision of:

·       - Prof Van Vliet;

·       - Prof Jongyoon Han, SMART Principal Investigator; and

·       - SMART Singapore co-Investigator and main PhD supervisor, Prof Lim Chwee Teck from National University of Singapore (NUS).

Other authors include SMART co-Investigators - Associate Professor Jerry Chan from KK Women’s and Children’s Hospital (KKH)
and G. Shivashankar from NUS; SMART Research Scientist Dr Zhiyong Poon; and SMART researchers L.M Nyan and T. Kaushik.

Dr Jacky Lee said, “Currently, researchers try to isolate MSCs based on protein markers found on the cell surfaces. But these
markers lack sufficient ‘resolution’ to distinguish between subpopulations of MSC with distinct functions. This approach
to identify subpopulations of stem cells, distinct from other marrow stromal cells, has re-ignited hope for better stem-cell treatments.”

SMART Research Scientist Dr Zhiyong Poon [潘志勇], said: “We are in the process of starting clinical trials on the use of biophysically
sorted cells for bone marrow regeneration and repair.”

Associate Professor Jerry Chan [陈国贤副教授], who is also Director, KK Research Centre and Senior Consultant, Department of
Reproductive Medicine at KKH [竹脚妇幼医院研究中心主席兼生育医药部门资深顾问医生], said, “This important discovery will allow us
to identify and select the best population of stem cells that we can use for treating different diseases such as brittle-bone disease or
in repairing large bone defects. We anticipate that this technique will enhance our knowledge of the cells being used in our upcoming
clinical trial to repair large bone defects.”

Better regeneration
The researchers tested injected MSCs in mice and found that these cells could repair both muscle and bone injuries, while marrow-derived
cells identified as osteogenic stromal cells were able to repair bone but not muscle.

Dr Hui Shi said, “Our test in mice showed that MSCs can be identified and highly enriched for bone growth and muscle repair. This means
that we can select, purify and concentrate MSCs for tissue repair for people who, for instance, suffer from knee joint pain.”

Going forward, the SMART team hopes to develop high-speed methods for separating MSC subpopulations. This research is funded
by the Singapore National Research Foundation, Prime Minister’s Office, under its Campus for Research Excellence And
Technological Enterprise (CREATE) programme.



About Stem Cells
•    Immature cells that have genetic material that moves around inside the nucleus, producing  more fluctuations of the nuclear cell membrane.
•    Have less rigid cytoskeletal structure than those of highly differentiated cells, at least when adhered to materials such as glass, making those attached cells seem less stiff.

About Mesenchymal Stem Cells (MSCs)
•    Immature cells that can differentiate into cells that produce bone, cartilage, fat or muscle
•    Resides deep within the bone marrow
•    Make up only a small percentage of cells in the bone marrow

About Osteogenic Stromal Cells
•    Resides deep within the bone marrow together with MSCs
•    Have already begun the developmental path towards becoming cartilage or bone-producing cells

About Stem-cell treatments (bone, muscle, cartilage)
•    MSCs are currently being investigated for a range of clinical applications such as bone repair, vascular insufficiency, cardiac failure, graft-versus-host disease, diabetes and others.