Creating body parts from scratch… that sounds like something straight out of Frankenstein. But what if I told you that researchers have been creating body parts since 1985?
Tissue engineering, a term coined in 1985 by bioengineer Yuan Chen-Fung, is a field of regenerative medicine that integrates the skillsets of biologists, physicians, and engineers to create or reconstruct human tissue.
So, how does it work?
Tissue engineering consists of two main components: a group of cells and a mechanical scaffold.
Cells have three main functions in tissue engineering:
- Create an extracellular matrix
2. Maintain that matrix
3. Function as tissue
Why are we using cells instead of non-living material? Cells have the ability to respond to internal and external stimuli, a characteristic which allows the engineered tissue to survive in a constantly changing environment.
The group of cells must share the same characteristics and functions as the tissue they aim to replace.
Think about it like parts of a car. If you want to replace the windshield wipers, buying new tires won’t help you. Similarly, if you want to replace keratinocytes (skin cells), growing myocytes (muscle cells) won’t help you.
But how do we find cells that can grow into the cells we want to replace? Stem cells!
Stem cells can develop into almost any desired type of cell, but there are different types of stem cells. Let’s go over a quick summary of each type.
These cells can vary in terms of origin, differentiation potential, and morphology:
Origin: Where the cells come from. Stem cells can either be endogenous (come from within the host) or exogenous (come from outside the host).
Differential potential: Differentiation is the process by which a stem cell changes to a more specialized type of cell. For example, it is the process by which a pluripotent stem cell turns into a blood cell or a neuron. Not all stem cells can turn into any type of cell, however. Many stem cells can only mature into different cell types of one specific tissue.
Morphology: Morphology refers to the structure and function of a biological organism or entity. The function of different types of stem cells can differ.
Types of stem cells
- Embryonic stem cells: Obtained from blastocysts, which is a hollow ball of cells that forms after fertilization. These stem cells are pluripotent, which means they can grow into any cell type in the human body.
In terms of tissue engineering, embryonic stem cells are exogenous, as they are generally derived from unused blastocysts created from in vitro fertilization (IVF).
- Tissue-specific stem cells: More specialized than embryonic stem cells, these stem cells can generate any type of cell specific to the tissue they are located in. For example, hematopoietic (blood-forming) stem cells (shown above), which are located in the bone marrow, can differentiate into red blood cells, white blood cells, and platelets. They cannot, however, differentiate into nerve cells or muscle cells. These cells are responsible for replacing frequently lost cells, such as the cells in the skin or the gut.
In terms of tissue engineering, tissue-specific stem cells are endogenous as they can be derived from the tissue recipient’s body. However, they have limited differentiation potential as they can only turn into certain types of cells.
- Induced pluripotent stem cells (iPSCs): Tissue-specific (adult) stem cells that were engineered in a lab to possess the properties of pluripotent stem cells. Since they are still so new (they were first discovered in 2006), much is still unknown about their potential negative effects, so they are not currently used in tissue engineering.
Currently, endogenous tissue-specific stem cells are used to grow the extracellular matrix necessary for tissue engineering.
Now let’s talk about the second main component of tissue engineering: a mechanical scaffold.
A scaffold is used to provide support to the cell tissue and to help shape the 3-D framework.
Think of the scaffold like a trellis and the cell tissue like a vine. A trellis gives a vine shape and structure to make it look pretty. Similarly, a scaffold gives cell tissue a shape and structure to make it functional.
Scientists have recently developed biodegradable scaffolds, which dissolve once the cell tissue deposits around them. Scaffolds can also help repress the body’s immune response.
Cool, so now we know that tissue engineering works by growing cells using a scaffold. But what does this have to do with creating a cornea?
Well first, what is the cornea?
The cornea functions as a window, which controls and focuses the entry of light into the eye.
Why is corneal tissue engineering important?
- Over 10 million people currently experience bilateral corneal blindness, and corneal transplants are expensive, costing between $13,000 to $27,000 per eye. In contrast, artificially engineered corneas could restore peoples’ vision for much cheaper.
- Corneal models can also allow scientists to study new drugs and gene delivery approaches, which will reduce the need for testing on animals
How does corneal tissue engineering work?
Dr. Elizabeth Orwin, a Professor of Engineering at Harvey Mudd University, takes a four-pronged approach to corneal engineering:
1. Matrix Structure & Composition
- Collagen sponges act as a scaffold for the engineered corneal tissue
- These sponges were found to contribute to light-scattering properties in the cornea
- Electrospinning is now used to create highly aligned, small diameter fibers to prevent light scattering
- Matrix stiffness is also an area of investigation, as the cornea in the body is very stiff
2. Mechanical Signals
- Engineered corneal cells that are not subject to any tension (mechanical signals) differentiate into myofibroblasts, which is a wound-healing phenotype of corneal cells.
- Wound healing phenotype: The protein expression that a corneal cell takes on when the cornea is injured
- Normal corneal cells express the protein crystallin, which is what allows a cornea to be transparent. Myofibroblasts do not express crystallin, which makes the engineered corneal tissue hazy.
- Dr. Orwin’s lab created a bioreactor to simulate the forces that exist on real corneal tissue, which allows the engineered corneal cells to produce crystallin
3. Electromagnetic (EM) Signals
- Dr. Orwin’s lab is also investigating the impact of electromagnetic signals on corneal cells growing in a culture
- They’ve found that high-intensity blue light is potentially impactful in activating the quiescent corneal phenotype to start dividing
- Quiescent corneal phenotype: When corneal stem cells are not dividing but can re-enter cell proliferation. After being signaled (like blue light can do), these stem cells can start dividing again.
4. Chemical Signals
- We’ve already established that corneal cells not subject to any mechanical tension alter their phenotypes to wound-healing phenotypes.
- For example, engineered corneal cells express ɑ-smooth muscle actin → this leads to the engineered corneal cells becoming hazy
- Normal corneal cells express high levels of TKT and ALDH1 (types of proteins)
- Goal: For the engineered cells to express TKT and ALDH1 and to minimize their expression of ɑ-smooth muscle actin
- qR-T PCR, Western blots, and confocal microscopy are used to analyze the levels of these proteins in cells
If you can somehow manage to get all four of the factors exactly right, you’ve got yourself a brand-new cornea!
Just kidding.
After reading this article, I hope you’ve realized how intricate and interconnected the process of creating a cornea is. This article was just a short and simplified glimpse into a few of the the factors biological engineers must take into account while crafting corneas.
You have to create conditions that are almost identical to the human body outside of the human body. You have to keep track of everything from the material you use to grow your engineered cornea in, to the pressure the cornea is subjected to, to the types of proteins the corneal cells express!
Despite the plethora of challenges they face, researchers are hopeful that tissue engineering will help reduce the cost of organ transplants and the need for animal testing.
If you have any questions, please connect with me on LinkedIn, or email me at hello@juikhankari.com.
Sources:
