Musculoskeletal Archives | Replacing Animal Research

The Problem

Musculoskeletal disorders are one of the leading causes of disability worldwide and most research into them relies on animals. Human-relevant models are being developed but there are barriers. Due to the invasive nature of collection, and the availability of donors, suitable cells like bone marrow mesenchymal stem cells can be difficult to obtain.

Patient-derived human cells also have a limited life span, and genetic modification is challenging. A potential alternative source is induced pluripotent stem cells (iPSCs). These are genetically engineered stem cells derived from adult human cells, like skin cells. They offer an alternative unlimited supply cells for use in human in vitro models of bone.

Bones are incredibly reactive to changes in load bearing. For example, daily walking induces stronger and greater bone formation, while a lack of mechanical stimulus leads to bone density loss. Any model system of human bones therefore needs mechanical stimulation.

The Project

Meilinda set out to see if nanovibrations (mechanical stimulation on a tiny scale) can:

Improve bone cell differentiation: help stem cells more effectively make bone cells

Mimic natural bone formation: replicate how bone cells develop in the body

Why nanovibrations?

Nanovibrations are an easy stimulus to use, and a simple system any lab doing tissue culture can adopt.

How does it work?

They grow the cells in standard lab dishes or flasks. These are then placed on top of a device called a bioreactor that creates the nanovibrations.

In essence, Meilinda is investigating whether these subtle vibrations can act as a simple yet effective way to encourage stem cells to develop into bone tissue, mimicking natural processes within the body.

Meilinda first differentiated induced pluripotent stem cells into induced mesenchymal stem cells (iMSCs), which she then checked for their ability to make osteoblasts, the cells that form new bones and grow and heal existing bones.

She grew these mesenchymal stem cells in the presence and absence of nanovibrations and then took samples to see if the cells were switching on bone-specific genes and making the appropriate minerals and proteins, such as collagen.

She successfully showed that nanovibrations do indeed enhance the differentiation of mesenchymal stem cells into osteoblasts, demonstrating the value this simple lab set-up can add to bone research.

The Potential

Meilinda grew bone cells from commercially available induced pluripotent stem cells using a simple set-up in a standard tissue culture lab.

The ability of nanovibrations to mimic mechanical stimulation means that a cell-based system that mimics the complex and dynamic nature of bone tissue is an accessible option for other cell culture labs too.

She had hoped to compare her stem cell-derived system with mesenchymal stem cells donated by patients, but there were no donors available during her project. This demonstrates one of the key reasons why a sustainable source of bone cells is so sorely needed.

Meilinda’s project has shown how the ultimate goal of a 3D model that combines both bone and cartilage cells, mimicking the structure and dynamics of real bones, might be achievable.

She also suggests that as nanovibrations enhance the differentiation of osteoblasts, they may not only be a replacement of animal ‘models’, but also have potential as a form of treatment for bone-related diseases such as osteoporosis, or to improve fracture healing.

Advancing in vitro bone model using human iPSCs and nanovibration

Meilinda Lesmana

Supervisor: Dr Carmen Huesa

Awarded: £1,000

The Problem

The Project

The Potential

Our funded projects

Creating a human-relevant bleeding simulator to replace the use of pigs

Growing human skin cells in low-calcium conditions for wound infection models

Creating human bone marrow models to understand treatment-resistant blood cancer