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Growing a Heart in the Lab
IBN Researchers Turned Human Embryonic Stem Cells into Heart Cells

Singapore, August 12, 2011 – The push towards growing organs for transplantation has received a boost from the latest discovery by the Institute of Bioengineering and Nanotechnology (IBN), the world's first bioengineering and nanotechnology research institute. Researchers from IBN have shown that human embryonic stem cells (hESCs) can be transformed into heart cells using a 'decellularized' heart as a scaffold.

Every day, 15 people die from heart disease in Singapore, which accounted for 31.6% of all deaths in 2009.¹ Worldwide, the number of severe heart failure patients waiting for transplant far exceeds the number of available donor hearts. The severe shortage of available donor hearts necessitates the development of other options for heart replacement. Now, with IBN's research breakthrough, we are one step closer to growing a new replacement heart from human embryonic stem cells.

Every organ in the human body has a scaffold or a structure, which provides it with its shape, and within this scaffold are many different types of cells with different functions. Tissue engineering aims to create the organ scaffold – either through the use of synthetic materials such as polymers, or through decellularization, which uses the whole organ as a scaffold after removing its cells.

Decellularization is ideal for tissue regeneration because it preserves the three-dimensional structure of the organ and the extracellular matrix (ECM) – the framework between the cells – that are complex and difficult to mimic. While current methods use specific ECM proteins to transform stem cells into a particular cell type, scientists have found it difficult to imitate the natural ECM.

Using the decellularization approach, a team of researchers led by Dr Andrew Wan, IBN Team Leader and Principal Research Scientist and Dr Karthikeyan Narayanan, Senior Research Scientist and Project Leader, removed the cells from the heart of a mouse and implanted the empty heart scaffold with hESCs to observe if these cells could attach to the scaffold and develop into heart cells. After 14 days, the cells developed into two different types of cells found in the heart: cardiac marker expressing cells and endothelial or blood vessel cells.

The cell-laden scaffold was then implanted back into the mouse where it was observed to develop visible blood vessels. The formation of blood vessels in the scaffold is critical for the transport of nutrients and oxygen to the heart, and has posed a major challenge in tissue engineering.

Dr Wan explained, “By exploiting the intact scaffold of a heart, we have directed the differentiation of human embryonic stem cells into cardiac cells. This study is the first proof-of-concept that addressed the complexity of obtaining different cell types in a scaffold using stem cells. The positive results we have derived encourage us to take this one step further, to achieve functional cardiac cells, and bring whole organ regeneration to the next level.”

Professor Jackie Ying, IBN Executive Director, added, “IBN's Cell and Tissue Engineering research is actively developing bioartificial organs using a combination of stem cell technology and biocompatible materials as alternative treatments for organ failures.”

Published recently in a leading peer-reviewed journal, Biomaterials, this new finding could pave the way to the development of a bioartificial heart, and realize the decellularized organ approach for organ transplantation. If successful, xenogeneic organs – animal organs seeded with human stem cells – could then be explored as a feasible alternative for regenerative medicine.

¹Source: Singapore Heart Foundation

Images Available on Request:

Figure 1: The IBN research team comprising Dr Shujun Gao, Serina Ng, Dr Andrew Wan and Dr Karthikeyan Narayanan (from left to right).

Figure 2: Decellularization of the mouse heart using detergent (SDS and Triton) to remove the cells.

Figure 3: A heart with visible blood vessels and newly-formed tissue is obtained by seeding a heart scaffold with stem cells.

Reference:

1. S. L. J. Ng, K. Narayanan, S. Gao and A. C. A. Wan, “Lineage Restricted Progenitors for the Repopulation of Decellularized Heart,” Biomaterials, (2011) DOI: 10.1016/j.biomaterials.2011.06.065.

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About the Institute of Bioengineering and Nanotechnology

The Institute of Bioengineering and Nanotechnology (IBN) was established in 2003 and is spearheaded by its Executive Director, Professor Jackie Yi-Ru Ying, who has been on the Massachusetts Institute of Technology's Chemical Engineering faculty since 1992, and was among the youngest to be promoted to Professor in 2001.

In 2008, Professor Ying was recognized as one of “One Hundred Engineers of the Modern Era” by the American Institute of Chemical Engineers for her groundbreaking work on nanostructured systems, nanoporous materials and host matrices for quantum dots and wires.

Under her direction, IBN conducts research at the cutting-edge of bioengineering and nanotechnology. Its programs are geared towards linking multiple disciplines across engineering, science and medicine to produce research breakthroughs that will improve healthcare and our quality of life.

IBN's research activities are focused in the following areas:

• Drug and Gene Delivery, where the controlled release of therapeutics involve the use of functionalized polymers, hydrogels and biologics for targeting diseased cells and organs, and for responding to specific biological stimuli.

• Cell and Tissue Engineering, where biomimicking materials, stem cell technology, microfluidic systems and bioimaging tools are combined to develop novel approaches to regenerative medicine and artificial organs.

• Biodevices and Diagnostics, which involve nanotechnology and microfabricated platforms for high-throughput biomarker and drug screening, automated biologics synthesis, and rapid disease diagnosis.

• Pharmaceuticals Synthesis and Green Chemistry, which encompasses the efficient catalytic synthesis of chiral pharmaceuticals, and new nanocomposite materials for sustainable technology and alternative energy generation.

IBN's innovative research is aimed at creating new knowledge and intellectual properties in the emerging fields of bioengineering and nanotechnology to attract top-notch researchers and business partners to Singapore. Since 2003, IBN researchers have published over 680 papers in leading journals.

IBN also plays an active role in technology transfer and spinning off companies, linking the research institute and industrial partners to other global institutions. The Institute has a portfolio of over 720 patents/patent applications on its inventions, and welcomes industrial partners to collaborate on and co-develop its technologies. IBN has successfully commercialized 33 patents/patent applications.

IBN's current staff strength stands at over 170 scientists, engineers and medical doctors. With its multinational and multidisciplinary research staff, the institute is geared towards generating new biomaterials, devices, systems and processes to boost Singapore's economy in the medical technology, pharmaceuticals, chemicals, consumer products and clean technology sectors.

IBN is also committed to nurturing young talents. Besides the training of PhD students, IBN has a Youth Research Program (YRP) for students and teachers from secondary schools, junior colleges, polytechnics, and universities. Since its inception in October 2003, IBN's YRP has reached out to more than 44,000 students and teachers from 265 local and overseas schools and institutions.

For more information, please log on to: www.ibn.a-star.edu.sg