Basics on Regenerative Medicine

Med Piper Technologies Pvt Ltd and Journo Med conducted an academic session on the “Basics of Regenerative Medicine’ in association with IMA medical networks jubilee units, serotonin units, Amala Institute of Medical Sciences and ISA Thrissur city branch. 

Ms Likitha Raja, M.Sc. Nanobiotechnology from Amrita Viswa Vidhyapeetam is giving us a basic understanding of regenerative medicine which is about to focus on the future. Ms Likitha is a nanobiotechnology graduate interested in the area of stem cells and regenerative medicine. Regenerative medicine is not much easy as it sounds because one needs to know the basics about stem cells if study in this field. If we combine stem cells with regenerative medicine, it gives solutions to many curable diseases. Studying regenerative medicine by improvising stem cells, always amazes and drifts. She has been inclined towards this field since her post-graduate final year and thus helped her to opt for her final year project.  

Regenerative Medicine in Basic

It’s an emerging interdisciplinary field that applies the principles of biology and engineering to the development of viable substitutes that restore, maintain or improve the function of human tissues.

Goals of Tissue Engineering 

• • Saves lives
  • Replace a structure with a complete living structure
  • Improve or replace tissues such as 
  • Tissue
  • Skin 
  • Muscle 
  • Bone 
  • Improve or replace organs such as the Heart, Kidney and Liver
    
    Regenerative Medicine seeks to replace a tissue or organ, it can be damaged by disease or trauma etc. One of the promising goals of regenerative medicine is to give permanent solutions for damaged tissue or organs under the same life.  

History of Regenerative Medicine

When the term “Regenerative Medicine” was established. The techniques or the methods the ancestors have used.  Around 700 BC Prometheus was a Greek Mythologist who was well known as the “Titan God of the Fire.” He poured fire on people, and he got punished by the Jews. Like a lifelong cycle of mystery where his liver, pecked out by an eagle, would regenerate each day to prolong his suffering. The people were not able to understand because it got regenerated each day. Now, the current statement is if one cuts away half of the liver, it will grow back in around a year. The liver is a unique organ in our body, even if one removes 90% of the liver, it can regenerate. Because liver stem cells got hepatocytes, they can be able to adapt to that environment. It can divide until the work starts growing completely. That’s why it’s a unique organ in our body. 

Cell Supportive Scaffold Guiding Regeneration

Egyptians around 1500 BC treated skin wounds using lint (soft material made from linen), grease and honey. Honey here acts as an antibiotic and grease here acts as a barrier that prevents the growth of pathogens. Lint is used as a scaffold to treat the wound.
Skin Grafts as early as 2500 BC with Susruta, the Father of Plastic Surgery, one of the most famous and most ancient physicians. He treated the mutilations (the act of removing the severely damaged organ from the body) of the ear, nose and lip. 

Dentistry tools were around 6500 years ago in Slovenia. The scientists have treated the tooth cavity filled with beeswax. 

The healing of Justinian was recorded as one of the historical references to regenerative medicine. The portrait painting was done by Fras Angiyes titled healing of Justinian where the two physicians were transforming the homograft lymph of a wounded soldier. Homograft means the tissue grafted from the same donor. The tissue graft of the donor is from the same species. The lymph tissue is taken and transplanted to the wounded soldier. 

Another example is a portrait painting of Gaspare Tagliacozzi from the University of Bologna. He is an Italian surgeon famous for reconstructive surgery in 1960, especially during rhinoplastic surgery, where the flap of the skin from the forearm is taken and attached to the nose. 

Modern History in Regenerative Medicine  

Rudolf Virchow, a Father of Pathology stated that tissue regeneration is completely dependent on the proliferation of the cells. That is very true because, without proliferating capacity, the stem cells can regenerate the tissue in 1858. The tissue won’t regenerate. In 1912, Alexis Carrel established and standardized the different tissue culture techniques. In 1930, the scientist has established an ex vivo perfusion culture of organs.

Perfusion culture means it likes a cell culture device and there is no need to do a manual media change for that. There would be a continuous media exchange itself. It is used to get a high-density cell. So, it is very much important nowadays. During 1939-1945 during the second world war, it resulted in scientific advancement in the field of materials. 

The first recorded use of the term “regenerative medicine” as it is currently understood, was in an article entitled, “Functional Organ Replacement: The New Technology of Regenerative Medicine,” published in Surgical Technology International in 1991.

Nowadays, tissue engineering began with the use of bioactive materials (known as scaffolds) to encourage tissue repair. Till around the 1980s, the term tissue engineering was loosely applied to the use of prosthetic devices (using plates, devices and sutures are man-made materials) and the surgical manipulation of the tissues. 

Regenerative Medicine -Today

A mouse had an ear-shaped structure on its body. A laboratory mouse named Swakenti where an ear-shaped structure developed on its body. It was formed by culturing the cow cartilaginous cells on the biodegradable ear-shaped implant. So, they cultured this technique in invitro conditions and after implanting the ear-shaped biodegradable scaffold underneath the skin of this mouse after some time they observe that this ear-shaped structure is grown outside the body. So, they discovered the collaboration of stem cells and scaffolds. This was done by a scientist named Charles A vacant.

Overview of Regenerative Medicine 

It is a combination of stem cells, scaffolds, growth factors etc. So, here the cells are isolated from the human body from the host and then we are expanding the cells in in vitro conditions. After expansion, we are ceeding these cells onto the scaffold. It can be any type of scaffold. The scaffold should mimic the invivo environment. It is a material that provides structural and functional support to proliferate, attach and migrate. It should mimic the extracellular matrix (ECM) inside our body which is the main purpose of using the scaffold. By making the scaffold, we are combining the growth factors, we can make the construct, and the construct is held back onto the regenerative areas. This is the overview of regenerative medicine. So, all the concentrations in the field of regenerative medicine.

Cellular Therapies 

Only possible by using stem cells. Without stem cells, it is not possible. Combining stem cells can be curable for many diseases, and there are also many types of stem cells in our bodies. 

Artificial Organs

The main advantage of using these artificial organs is if anyone wants to study in detail about a specific organ. Anyone can create a miniature organ in invitro conditions by using a few types of stem cells and it can study the complete mechanism of a specific organ and can be used for developing drugs that can be used as therapeutic models nowadays. 

Cellular therapies using Stem Cells

Stem cells act as specialized cells inside our body for regenerative purposes. It can replicate itself and it can also differentiate into many other cell types not bound. It can give a solution to many incurable diseases. 

Different levels of Differentiation Potential

Each kind of stem cell has a different level of potency. The level of differentiation potential means the ability of the cell to differentiate into another cell type i.e. the differentiation potential. So, there are some levels of potency i.e. totipotency, pluripotency, unipotency and multipotency. 

Totipotent: 

Capable of giving rise to any cell type in our body. The best example is the zygote, the fertilized egg. 

Pluripotent:

Capable of giving rise to many cell types. 

It cannot develop into an organism. 

An example of this is the Inner cell mass of the blastocyst.

Multipotent:

Can give rise to multiple, but a limited number of lineages. 

Committed to producing specific cell types and specialization potential is limited to one or more cell lines. 

The best example is adult stem cells: MSCs 

Unipotent:

It can only make only one cell type. 

I.e., Liver stem cells i.e., hepatocytes. 

Types of Stem cells 

Embryonic stem cells

An embryonic stem cell is isolated from the inner cell mass of the blastocyst. The embryonic stem cell is also called pluripotent stem cells. So, the blastocyst is formed from the fertilized stem cell i.e. zygote that develops into a fertilized 4-celled staged blastocyst and the 8-celled stages into the ball of cells called “ Blastocyst.” The blastocyst has two cell types i.e. trophoblast, and inner cell mass. The pluripotent stem cells have an inner cell mass and they can be expanded in in-vitro conditions. 

Induced Pluripotent Stem Cells

Induced pluripotent stem cells are derived from somatic (adult, non-germline) cells, which have been reverted to an embryonic stem cell-like state. 

The process of creating these cells often referred to as “reprogramming” involves introducing a combination of three to four genes for transcription factors. 

Adult stem cells

These stem cells are found in small numbers in most adult tissues, such as bone marrow or fat. 

Compared with embryonic stem cells, adult stem cells have a more limited ability to give rise to various cells of the body. 

The primary roles of adult stem cells are to maintain and repair the tissue in which they reside. Adult stem cells are rare and generally small in number, but they can be found in several various tissues of the adult organism. The most common example is MSCs.

What is Cell Differentiation?

• Differentiation is the process by which cells become specialized and take on specific roles in an organism. 
• Dedifferentiation involves a terminally differentiated cell reverting to a less differentiated stage from within its lineage. 

Scaffold

The scaffold is an extracellular matrix of tissue model construct. 

Learning from Nature- Biomimicry 

To imitate nature, we need to 

 Understand the basic biology of the tissues and organs of interest

Develop methods for the control of these processes

Develop strategies for engineering the tissue substitutes or tissue repair and regeneration.

Scaffold Requirement

Biomaterials

In the first consensus conference of the European Society for Biomaterials (ESB) in 1976, a biomaterial was defined as a nonviable material used in a medical device, intended to interact with biological systems. 

ESB’s Current Definition is 

Material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body. 

• Biocompatibility 
• Biodegradability 
• Mechanical properties
• Scaffold Architecture

Why do we apply Nanotechnology in Regenerative Medicine?

By using electrospinning scaffolds can be created, and nanofibrous scaffold and microfibrous scaffolds can be created. Upon the solution used, the scaffolds can be created. Regenerative medicine is a methodology, and nanotechnology is a tool. 

Typically, there are three individual groups of biomaterials which are used in the fabrication of scaffolds for tissue engineering. They are:

Natural polymers, Synthetic polymers and ceramic scaffolds. 

Artificial Organs 

An Artificial Organ is a human-made organ device or tissue that is implanted or integrated into a human. 

• Providing life support to prevent imminent death while awaiting a transplant. (eg: artificial heart)
• Dramatically improving the patient’s ability for self-care (eg: artificial limb)
• Improving the patient’s ability to interact socially. (eg: cochlear implant)
• Improving patients’
• Quality of life through cosmetic restoration after an accident. 

Organoid

It is a miniaturized and simplified version of an organ produced in in vitro conditions that shows realistic microanatomy. They are derived from one or a few stem cells. 

Conclusion 

One can come across a few basics of regenerative medicine through the study.