Organ regeneration with drugs

A drug that had been discarded reveals its ability to rebuild organs damaged by disease or injury.

IN SUMMARY

Stem cell treatments make headlines about healing and regeneration of various parts of the body, but they have had little success.

The compound MSI-1436 appears more promising, as indicated by animal experiments. It removes the brake on the body’s natural ability to regenerate cells.

The molecule, originally intended for the treatment of diabetes and obesity, successfully passed safety tests in people, a huge advantage in drug development.

YOU MAY ALSO LIKE

Regenerative medicine

An account of shark bites in a Scottish tavern opened us up to new ideas about rebuilding damaged organisms. At the beginning of this century, Georgetown University geneticist Michael Zasloff gave a lecture at the University of St. Andrews on various natural antibiotics found in animal skins. After the talk, he went to have a drink with other academics, and a marine biologist commented that dolphins were frequently attacked by sharks, causing huge injuries, 45 centimeters long and 12 centimeters deep. Surprisingly, the dolphins were cured within weeks, with no signs of infection.

Amazed by such speed to recover from excruciating injuries, Zasloff couldn’t stop thinking about that conversation. In the years that followed, he read reports on bitten dolphins and spoke with marine biologists who studied these animals. In 2011 he published a letter in the Journal of Investigative Dermatologyentitled “Observations on the extraordinary (and mysterious) wound healing of the bottlenose dolphin.” In it, he pointed out that the dolphins did not seem to just mend the tear with a scar, which produces other types of cells, but actually regenerated the damaged tissue. Soon after, he called one of us. Strange, then president of the Mount Desert Island Biology Laboratory (MDIBL) in Maine, was pushing for research into natural and synthetic compounds that stimulate regeneration, and Zasloff thought that some of the antibiotics he had discovered in animal skin also could encourage this kind of recovery. Anything that contributes to replenishing or restoring cells destroyed by disease or injury would be a medical breakthrough.

RELATED CONTENT

  • Limb regeneration
  • Challenges of regenerative medicine
  • Advances in regenerative medicine

Six years after that call, the three of us (Yin, Strange and Zasloff) have shown that the natural antibiotic MSI-1436, discovered by Zasloff in a small shark, intensely stimulates the regeneration of various damaged organs in zebrafish and the heart muscle. on the mouse. The compound releases certain molecular “brakes” that suppress the natural ability of tissue to regenerate after injury. In mice affected by the equivalent of muscular dystrophy in humans, it slows down the degeneration of the muscles. We are still experimenting with animals and have not demonstrated these effects in humans, but MSI-1436 has a significant advantage over the myriad compounds that show promise in the lab and then fail in people – it has already proven its safety.

Brain waves detected in mini-brains

A new method of stem cell culture has resulted in a network of neurons complex enough to produce electrical activity.

  • Sean Bailly

Section of a cerebral organoid. Each color corresponds to a different type of brain cell. [Muotri Lab / UCTV]

With some 86 billion neurons, the brain is a particularly difficult organ to study. One solution is to investigate a simplified system with fewer neurons. In 2013, Madeline Lancaster’s team from the Vienna Institute for Molecular Biotechnology created miniature brains, also known as brain organoids, from human stem cells in the laboratory.

Although these mini-brains are very useful to researchers, until now they have never observed electrical activity in them. Now they have. Alysson Muotri of the University of California, San Diego, and her team have improved organoid harvesting techniques and discovered that, after a period of development, brain waves similar to those seen in the brains of babies appear spontaneously premature

It was known that in the brains of these babies the electrical activity shows chaotic patterns. But what happened before, that is, how complex neural activity arises and develops, was completely unknown. Furthermore, although the work with rodents had made it possible to observe the activity of immature brains, the question arose as to whether this could be extrapolated to the human brain.

RELATED CONTENT

  • Brains created in the laboratory
  • Organoids: The Body Builders
  • Small artificial brains to investigate

Brain organoids offer an opportunity to study such questions. About the size of a pea, they are obtained from pluripotent human stem cells. If placed in an environment that reproduces the conditions in which the brain develops, these cells differentiate and form neurons that organize themselves in a three-dimensional structure. This results in a reduced and simplified version of the human cortex (brain region involved in the cognition and interpretation of sensory information). Building on previous work that had produced mini-brains without electrical activity, Muotri’s team refined the technique, allowing them to track hundreds of organoids for ten months.

The researchers first showed that organoids harbor the same cell types and proportions as human brains at the same stage of development. They also recorded the electrical activity of the organoids using multiple electrode arrays. Within a few months, the mini-brains produced activity never before seen in these systems. They were chaotic single-frequency electrical patterns, signals that are also detected in the immature brains of premature babies. Over time, the signals became more regular and more diverse in terms of frequency, a transition that indicates that mini-brains continue to develop as the number of neural connections increases.

Next, the authors created a deep learning program to study the formation of mini-brains. They used the brain wave recording of 39 babies born six to nine months after conception as a reference. By analyzing the signals from the organoids in different phases, the algorithm was able to predict the level of maturity of the minibrains. This confirms that human brains and organoids have comparable development. Therefore, the latter could be a model of great interest to study the development of the brain, but also diseases such as Alzheimer’s, epilepsy or autism, or to test drugs.

Despite this breakthrough, organoids remain rudimentary models and are a long way from representing the complexity of the human brain. The current work also raises ethical questions: from what moment can a miniature brain with brain activity be considered conscious? We still lack much knowledge about the brain to answer this thorny question.

Vascularized mini-kidneys are created from human stem cells

They develop in less than twenty days, and their structure and function resemble that of the kidney of a human fetus in its second trimester of gestation.

YOU MAY ALSO LIKE

Regenerative medicine

The generation of organoids, also called mini-organs, is one of the greatest scientific advances in regenerative medicine. These are artificially created three-dimensional cellular organizations that resemble, structurally and functionally, a human organ. This technique has great potential in cell therapy and tissue engineering. In addition, it is presented as an effective strategy for the exploration of new drugs or even to investigate disease models.

The mini-organs are created from stem cells that, under certain stimuli, divide, grow and end up building a complex tissue, similar to the organ from which they come. So far, organoids have been obtained from intestines, brains, and kidneys, among others. However, these artificial tissues have significant deficiencies, including the lack of blood vessels that allow the diffusion of nutrients and oxygen. This fact limits its growth and affects the final dimensions of the organoid.

Now, a group of researchers from the Institute of Bioengineering of Catalonia in collaboration with the Hospital Clínico de Barcelona, ​​the Higher Council for Scientific Research, the University of Barcelona and the Salk Institute for Biological Studies, in California, has just published in  Nature Materials  a method to obtain vascularized kidney organoids, formed in just twenty days. Since 2013, the year in which some of these scientists first generated kidney progenitors from pluripotent stem cells, they have managed to develop complex structures very similar to those of an embryonic organ.

RELATED CONTENT

  • Organoids: The Body Builders
  • Stomachs in a petri dish
  • Brains created in the laboratory

In this latest research, they have optimized the extracellular environment to fully reproduce the environment in which the kidneys develop in the human body. Thus, they have managed to accelerate the growth of stem cells to form mini-kidneys similar to those of the second trimester of fetal development.

One of the most notable discoveries of this publication has been the obtaining of mini-kidneys with blood circulation. Once the organoids were generated, in order to facilitate their vascularization, they were implanted in the chorionic membrane of chick embryos on the sixteenth day of their development. This tissue, which is the fetal part of the placenta, is rich in blood vessels. On the third day they observed that the organoids, which were inside the egg, had developed vascular endothelial cells and the embryo’s blood circulated inside the organoid.

Currently, the artificial generation of kidneys that can be transplanted is still a distant goal. However, these organoids have morphological and functional characteristics so close to those of a human kidney that they could serve as a model to study kidney dysfunction.

The data collected in this publication represent an important advance both in development and disease research and in the field of regenerative medicine, and presents a novel methodology applicable to other biological tissues.

Marta Consuegra Fernandez

Artificial bone culture

A new experimental model of living bone tissue is created.

YOU MAY ALSO LIKE

Organoids

OrganoidsMORE INFORMATION

the organoid Tiny masses of cells that mimic the anatomy and functions of an organ, grown in the laboratory, are becoming increasingly important in medical research. Micro-models of the brain, lungs, and other organs have existed for years, but models of bone tissue are very difficult to obtain. Bone is a separate issue because the different types of cells coexist immersed in an extracellular matrix, a network of collagen and minerals subject to continuous remodeling. Previous attempts to create a bone organoid have failed to closely mimic the way human bone cells form in parallel with that matrix and the interactions with it. However,

A study published in Advanced Functional Materialspresents the first organoid to incorporate a “unified view” of the early stages of osteogenesis (bone formation), according to lead author Anat Akiva, a cell biologist at Radboud University Medical Center. She and her collaborators discovered that by applying a mechanical force that simulates the stresses that shape bones in the human body, it is possible to cause bone marrow precursor cells to transform into osteoblasts (bone producers) and osteocytes (regulators). growth), which together make all the proteins they need to function. The devised process also led to the growth of an extracellular matrix very similar to that of human bone tissue. After four weeks of culture, the end result is a miniature cylinder of fibrous tissue,

RELATED CONTENT

  • They manage to create bones, muscles and cartilage with a 3D bioprinter

The new tool would serve to closely observe what happens on a molecular scale when the osteogenesis process fails and causes bone disorders that affect millions of people around the world. One of them is osteogenesis imperfecta, or “crystal bone disease,” a genetic disorder that weakens the extracellular matrix and causes hundreds of spontaneous fractures throughout life. Bone cancer such as osteosarcoma also alters bone formation and this new model would allow investigating the infiltration of tumor cells into the extracellular matrix and the extemporaneous manufacture of bone that they unleash.

Bone organoids could also help doctors create personalized treatments, says Ralph Müller, deputy director of the Institute for Biomechanics at ETH Zurich, who was not involved in the study. Before designing the treatment plan, organoids will be cultured from living tissue samples from the patient to explore how their bones would respond to various interventions.

“We have a reliable system for manufacturing bone tissue, with which we can fine-tune a lot, study exactly what is wrong and find out if there is a solution,” Akiva concludes.

WHAT IS REGENERATIVE MEDICINE AND ITS ADVANTAGE

regenerative medicine

Regenerative Medicine includes therapies that seek the regeneration of tissues and organs, including stem cell therapy.

This therapy has emerged as a new discipline that aims to replace, protect or regenerate damaged cells, tissues or organs. This type of medicine is linked to various fields of science, such as genetic engineering, tissue engineering, and cell therapy. 

Regenerative Medicine is a broad field that includes research on self-healing, that is, in which the body uses its own systems, sometimes with the help of foreign biological materials to recreate cells and rebuild tissues and organs .  

Unlike many traditional treatments, some high cost, with side effects that do not address the causes but the symptoms, cell therapy has had very promising responses.

AdobeStock_143341643

What is cell therapy?

It is a process by which new cells are introduced into the body to treat disease. Cell therapy involves a wide variety of cell types with regenerative, reparative, protective or immunoregulatory characteristics, among which are the so-called stem cells or Stem Cells. These cells can be obtained from various tissues such as fatty tissue, bone marrow, umbilical cord cells, umbilical cord blood, dental pulp, among others, to later be reintroduced into the individual by different routes, depending on the medical condition of the patient. patient.

What makes stem cells so special?

Mesenchymal stem cells or Mesenchymal Stem Cells (MSC) have the unique ability to differentiate or transform into cells with specialized shapes and functions. These have demonstrated in vitro the potential to differentiate into a variety of cells such as bone, cartilage, adipose tissue, musculoskeletal, cardiomyocytes, endothelium, hepatocytes, by islets – such as conglomerates, neurons, astrocytes and oligodendrocytes.

In BioXcellerator, the source for obtaining the stem cells used are those derived from adipose tissue, bone marrow and umbilical cord. Why?

They have unique advantages:

  • Easy to obtain
  • Absence of risk of immune rejection
  • Immediate availability
  • Minimal risk of complications, infections, and disability

The number of stem cells in our body decreases as time passes. Umbilical cords harbor undifferentiated cells, which is why they are a highly prized source.

L as characteristics and properties of stem cells MSC:

  • Capacity of numerous cycles of cell division maintaining the undifferentiated state or self renewal
  • They can differentiate into many types of specialized cells.
  • They are found in multiple tissues of the body.
  • One of its main functions is to maintain cell balance and replace cells that become diseased or dying (apoptosis) and under pathological conditions it has the potential to regenerate damaged tissue.
  • They are multipotent, that is, they can differentiate into a subset of cell types such as bone, cartilage, adipose tissue, muscle, endothelial cells, among others.
  • They synthesize and secrete a set of trophic factors (growth factors) and cytokines that stimulate or activate cells and promote their expansion or proliferation, among other functions.
  • They have the ability to migrate to the affected areas through inflammatory signals released under pathological conditions (Homming).

Clear your doubts: Myths and realities of stem cells 

Why have stem cell treatments?

In a natural way, our body has a capacity to repair injuries that diminishes as we age. The quantity and quality of MSC that we all have also decreases over time.

MSC treatment consists of supplying the patient with as many cells as possible, thus increasing the body’s ability to protect, replace or regenerate damaged or diseased cells.

Advantages of a stem cell treatment 

The characteristics and properties of stem cells  generate multiple advantages in this Regenerative Medicine treatment: 

  • It has little chance of generating rejection by the body.
  • It is an alternative treatment for medical conditions such as degenerative diseases, which do not have effective traditional pharmacological therapies.
  • MSCs offer treatments with an important possibility of recovery and improvement in life expectancy and quality.
  • They can reverse or slow the progression of the disease.
  • MSCs of adipose tissue and bone marrow are obtained through outpatient and low-risk procedures, under local anesthesia.
  • They can be used for rejuvenation or anti aging treatments.

Learn about the diseases that can be treated with this Regenerative Medicine therapy

If you want to know more about this cell therapy, stay with this free ebook that we prepare for you.