Tissue growth and stem cell therapy

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Tissue growth

Organ growing is one of the new advances in medicine that would enable organ replacement. Human organs will be replaced internally or externally, using a replacement organ that was "grown" using a tissue or a cell from the patient himself. This new technology will make possible a virtually inexhaustible supply of organ replacements, thereby doing away with the need to wait for organ donors and removing the risk of rejection of an implanted organ. In 1997 alone, less than 10% of the 40,000 patients in the US needing a heart got one. The statistics are more or less the same for those needing new skin, liver or kidneys.

Organ growing aims to combine different disciplines such as genetic engineering, medicine and biology to enable single cells to develop into new organs inside the patient or in a simulated environment. Scientists have already succeeded in the creation of artificial bone scaffolding which forms the base for bone cell growth. Future developments will involve growing complex organs such as the kidneys or heart.

Internal Organ Growing

Neo-organs or man-made organs have revolutionized the way patients are treated. One of the examples for internal organ growing is when biodegradable polymers are used as scaffolding materials for cells which are able to regenerate into whole tissues. The cells then replicate within the wound site and the scaffolding breaks down to be ejected as waste by the body. Another example is when a molecule is injected into an organ or a wound. The injected molecules then act as a migration site for the patient's other cells. These cells are then made to develop into the right kind of cell - that which is needed to heal the organ.

External Organ Growing

External organ growing has also proved successful as a new bladder has been grown using progenitor cells. This process used molds of structures called bioresorbable scaffolds in the shape of the required organ. The patient's own progenitor cells were identified and separated through a biopsy and placed in this scaffold to regenerate and grow into the needed organ. After maturing into a full sized organ, it was implanted into the patient where it worked as well as a perfectly health bladder. This process has already been tagged as a better alternative to Cytoplasty (a part of the intestine functions as the bladder) that leads to undesirable side effects and absorption of unwanted elements into the body.

Another method being researched today is using animals to grow human organs. This is done by extracting stem cells from the bone marrow of the patient. The stem cells are then injected into a sheep's fetus, enabling the sheep to integrate the human cells into its system. When the sheep is born, the organ developed can be harvested and implanted into the patient's body. Of course, there is a risk of the patient's body rejecting the organ, but the presence of the patient's own cells will go a long way into successfully integrating the organ into the body.

Replacement organ, tissues engineering.

In the future, tissue engineering and stem cell science will allow us to cure disease, regenerate body parts, even delay death. Such is the vision of ROBERT LANZA, the chief scientific officer at Advanced Cell Technology, a Massachusetts biotech firm that is a leader in developing cell-based therapies. The recent discovery that an engineered virus can restore an adult cell to its youthful condition by altering just a handful of genes—a technique called cellular reprogramming—brings his futuristic medical goals a bit closer to reality.

What is so significant about the new technique of cellular reprogramming? You're turning a terminally differentiated cell back in time to make it what's called an induced pluripotent stem cell. "Pluripotent" means it can become all the cell types in the body. Induced pluripotent stem cells are not controversial at all because you don't use embryos or cloning. You can take a skin cell from you, me, or anybody, and then introduce factors [proteins that initiate DNA transcription] into the cell that will turn it into a pluripotent cell. You can also introduce the cells into an embryo and they can contribute to the germline and be passed on to subsequent generations.

How could cell-based therapies help us create and transplant new organs?
The two hurdles for transplantation therapy in the last several decades have always been the shortage of cells and tissues, and rejection. Embryonic stem cells solve the supply problem, allowing you to generate an unlimited supply of cells. The problem that has not been solved is rejection, and that's where cloning or this new technology of cellular re-programming comes in—you are using the patient's own tissue.

What diseases do you expect to see treated with cellular therapies?

We recently published a paper on a type of cell we created called a hemangioblast, which exists only transiently in the embryo. With the ability to become all of the blood cells-including your immune cells, red blood cells, all of your blood system, as well as vascu-lature—hemangioblasts have been one of biology's holy grails. The point is, we can use transient, intermediate cells like hemangioblasts as a toolbox to fix the adult body so you don't have to amputate limbs from vascular disease, so you may not have to go blind, or so we can prevent heart attacks. We discovered that you can generate literally millions, or even billions, of these from human embryonic stem cells. No one had ever done that before. Then the question was "Okay, this is great. We got a cell in a petri dish. But what does it do? What can it do?"

Ischemia is what causes people with diabetes to lose limbs—because of the lack of blood, you lose toes, fingers, everything. Malcolm Moore at Memorial Sloan-Kettering Cancer Center has an animal model of ischemia. In these animals, if the femoral vein is severed, there is very minimal blood flow, like 10 to 20 percent. We injected hemangioblasts into the muscle of the damaged ischemic limb in a group of these animals. Within a month we found almost 100 percent restoration of the blood flow. I certainly wouldn't have expected that. I thought these cells were pretty amazing, but not that amazing.

You are also looking at growing blood from reprogrammed cells, right?
The military is concerned about a real crisis they may face. They don't have enough O-negative blood, the type that can be accepted by anyone who needs a transfusion. There is often not enough time for tissue matching in the battlefield environment. In the past they have had severe shortages and have had to fly in O-negative blood from Germany and other countries. They would like to build a machine they can put on a Humvee that will make all the blood they want. Now we can make literally 10 to 100 billion red blood cells from one little six-well plate. We're learning how to make platelets, to be used for clotting, for anyone in an emergency situation that needs to stop bleeding. That could have tremendous value.

We share the first floor of our building with the American Red Cross. Every day they have their signs out on the road looking for blood donors: "Urgent need for blood." In a few years, hopefully all they will need to do is simply say, "Okay, we're running low, make us up 100 units."

Will it be possible to engineer an entire new body part?
To realize the full potential of stem cells, we must learn how to reconstitute them into more complex tissues and structures. If we want to make an artery or bones or even an entire kidney or a heart, we need to learn to assemble and grow them on a biodegradable scaffold that the body can later absorb. You let the cells grow, and when you put them back in the body, the body reabsorbs the synthetic materials that are biodegradable and you're left only with the living tissue.

In the future, if you get in an accident and you lose a kidney, we'll take a skin cell and we'll grow you up a new one. This is not science fiction. The field is moving so fast that by the time anyone who is middle-aged or younger now is older, we will simply grow you a new kidney. What seems like science fiction and space age is going to become reality really quickly.

What about life span? Will these cells help us live longer?
If you look at the turn of the last century, peopie's life span was, on average, about 36. It is now double that. It turns out that human longevity plateaus as it approaches around 120 years—that is probably the maximum. Certainly by eliminating infectious diseases and some of the chronic diseases such as cancer, we can get over 100. What we're talking about is patching you back together like a bicycle tire up to 120 years. That was always my thinking. But now with these heman-gioblasts, I have questioned my own rules. These hemangioblasts can go in and fix the damaged tissue.

So, okay, you patch the body together, but then you're going to become senile. Now we're learning that we may be able to repair the damage in the brain itself, too. If this continues the way it looks like it's going, we may break that ceiling, like breaking the sound barrier. I'd be very hesitant to put a lid as to where longevity's going to go.

Article by PAMELA WEINTRAUB from Discover magazine (Summer 2009).

Tissue growth news: 
Jaw Bone Grown from Adult Stem Cells

Stem cells enable recovery from spinal injury

Paralysed rats have been enabled to walk again, by transplanting nerve cells derived from human embryonic stem cells into the animals. The findings add to a growing number of studies that suggest that embryonic stem cells could have a valuable role to play in treating spinal injuries. The researchers say trials on people using this technique could start in about two years time. Researchers are exploring a number of approaches to enable recovery from spinal-cord injury, including drugs that overcome spinal cells' reluctance to re-grow, ways of bridging the gap between severed nerves, and transplants of various tissues, including adult stem-cells derived from bone marrow, and nerve cells from the nose. Human trials of some treatments, such as that using nose cells, have already begun. But the first stem-call trials will be on patients with recent spinal cord injuries and localised damage; treating people who have been paralysed for years, or who suffer from degenerative nerve diseases, is more difficult. Ways will also have to be found to prevent people rejecting the stem cells. One possible alternative to immunosuppressant drugs would be to first give the patient bone-marrow stem cells from the same source as the nerve cells. This might trick the patient’s immune system into developing tolerance.


But adult cells have serious limitations as a mass-market treatment, because not many cells can be grown from a single source. That is not a problem with embryonic stem cells (ESCs). "One cell bank derived from a single embryo produces enough neurons to treat 10 million Parkinson's disease patients", says Thomas Okarma of the Geron company in California. What is more, adult stem cells may not be as versatile. "At this moment, there is very little hard evidence that a bone marrow stem cell can turn into anything but blood, or that a skin stem cell can become anything but skin", he says. ESCs, on the other hand, have the potential to develop into practically any type of tissue.But there is nevertheless a serious problem with ESCs. "Undifferentiated human embryonic stem cells have a very high probability of forming tumours," says Hans Keirstead at the University of California, Irvine, whose team has performed the latest research. To prevent this, his team turned ESCs into specialised cells before transplanting them. They transformed the ESCs into oligodendrocytes, the cells that form the insulating layer of myelin that is vital for conducting nerve impulses. Keirstead's team transplanted the oligodendrocytes into rats with "bruised" spines. After nine weeks, the rats fully regained the ability to walk, he says, whereas rats given no therapy remained paralysed. The team repeated the experiment on three separate occasions, with the same results. Analysis of the rats' spinal cords revealed that the transplanted oligodendrocytes had wrapped themselves around neurons and formed new myelin sheaths. The transplanted cells also secreted growth factors that appear to have stimulated the formation of new neurons.While many promising spinal repair experiments have proved hard to reproduce, researchers at Johns Hopkins University in Baltimore, Maryland, also announced similar results last week. The team injected undifferentiated human ESCs into rats with injured spinal cords. After 24 weeks, the treated rats could support their own weight. Team leader Douglas Kerr thinks the animals' recovery was not due to the growth of new cells, but to the secretion of two growth factors (TGF-alpha and BDNF), which protected damaged neurons and helped them to re-establish connections with other neurons. "The stem cells' magic was really their ability to get into the area of injury and snuggle up to those neurons teetering on the brink of death," says Kerr, whose results will appear in the Journal of Neuroscience.

Umbilical cord blood stem cells are used as a part of the therapy regimen for nearly 50 diseases today. One of the challenges in developing additional cellular therapies is the need to multiply and preserve large quantities of these powerful umbilical cord blood stem cells for use in treating an even broader range of diseases. These important studies indicate that we can substantially increase the number of these valuable cells and freeze them for later use", says Jan Visser of ViaCell.

Parkinson's disease treatment by Stem cell tharapy

In the future, if you get in an accident and you lose a kidney, we'll take a skin cell and we'll grow you up a new one. This is not science fiction.

ScienceDaily (Mar. 31, 2010)A Columbia scientist has become the first to grow a complex, full-size bone from human adult stem cells.

Gordana Vunjak-Novakovic, a professor of biomedical engineering at the Fu Foundation School of Engineering and Applied Science, reports that her team grew a temporomandibular joint (TMJ) from stem cells derived from bone marrow. Her work is reported in the online Early Edition of the journal Proceedings of the National Academy of Sciences this month.

"The TMJ has been widely studied as a tissue-engineering model because it cannot be generated easily, if at all, by current methods," says Vunjak-Novakovic, whose co-authors include Warren L. Grayson, then a post-doctoral student in her lab and now an assistant professor at Johns Hopkins University. Around 25 percent of the population suffers from TMJ disorders -- including those who suffer from cancer, birth defects, trauma and arthritis -- which can cause joint deterioration. Because the TMJ is such a complex structure, it is not easily grafted from other bones in a patient's body. "The availability of personalized bone grafts engineered from the patient's own stem cells would revolutionize the way we currently treat these defects," she says.

Current methods of treating traumatic injury to the jaw include taking a bone from the patient's leg or hip to replace the missing bone. "Wouldn't it be wonderful if we could get the patient's own stem cells and grow a new jaw?" says Dr. June Wu, a craniofacial surgeon at Columbia University Medical Center who advised Vunjak-Novakovic on her research.

Vunjak-Novakovic's technique for turning stem cells into bone was inspired by the body's natural bone-building process. Her team started by analyzing digital images of a patient's jawbone in order to build a scaffold into the precise shape of a TMJ joint. The scaffold itself was made from human bone stripped of living cells. The team then seeded the scaffold with bone marrow stem cells and placed it into a custom-designed bioreactor. The reactor, filled with culture medium, nourished and physically stimulated the cells to form bone. "Bone tissue is metabolically very active," she says. Bone tissue develops best when it is bathed in fluid flowing around it. Vunjak-Novakovic and the team looked into the exact flow rates one needs for optimal effects. After five weeks, they had a four-centimeter-high jawbone that was the precise size and shape of a human TMJ.

The technique can be applied to other bones in the head and neck, including skull bones and cheek bones, which are similarly difficult to reconstruct, but Vunjak-Novakovic started with the TMJ because, "We thought this would be the most rigorous test of our technique," she said. "If you can make this, you can make any shape."

Her team's next step is to develop a way to connect the bone graft to a patient's blood supply to ensure that the graft grows with the person's body. "Our bones change, and these biological grafts would change with us," says Vunjak-Novakovic.


Story Source: Adapted from materials provided by The Record, Columbia University. Original article written by Anna Kuchment.

 Journal Reference:
  1. W. L. Grayson, M. Frohlich, K. Yeager, S. Bhumiratana, M. E. Chan, C. Cannizzaro, L. Q. Wan, X. S. Liu, X. E. Guo, G. Vunjak-Novakovic. Regenerative Medicine Special Feature: Engineering anatomically shaped human bone grafts. Proceedings of the National Academy of Sciences, 2010; 107 (8): 3299-3304 DOI: 10.1073/pnas.0905439106
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