Blocking Differentiation is Enough to Turn Mature Cells into Stem Cells


Hiroshi Kawamoto led a collaboration between the RIKEN Center for Integrative Medical Science and other institutions in Japan and Europe that examined the possibility that adult cells can be maintained in a stem cell-like state where they can proliferate without undergoing differentiation. They discovered that in immune cells, blocking the activity of one transcription factor can maintain the cells in a stem cell-like state where they continue to proliferate and still have the capacity to differentiate into different mature cell types.

Kawamoto and his team genetically engineered hematopoietic progenitor cells from mice to overexpress the Id3 protein. Id3, or inhibitor of DNA binding 3, is an inhibitory protein that forms nonfunctional complexes with other transcription factors. In particular, Id3 inhibits so-called “E-proteins,” (such as TCF3) which drive the progenitor cells to differentiate into immune cells.

Overexpression of Id3, in addition to soaking the cells in a cocktail of cytokines, cause the cells to continue to divide as stem cells. However, when the cytokines were withdrawn, the cells differentiated into various types of immune cells.

Next, Kawamoto and his collaborators infused these engineered hematopoietic progenitors into mice that had been depleted of white blood cells. They discovered that their Id3-overexpressing cells could expand and replenish the white blood cell population of these.

In a follow-up experiment, Kawamoto and his crew recapitulated this experiment using human umbilical cord blood hematopoietic progenitors. Just like their mouse counterparts, these umbilical cord cells could be maintained in culture, and then, upon change of culture conditions, could differentiate into blood cells.

Because these cells can be kept in an undifferentiated state and can extensively proliferate, this culture system provides a model for studying the genetic and epigenetic basis of stem cell self-renewal. And it might also allow scientists to inexpensively grow large quantities of immune cells for regenerative medicine or immune therapies.

This work was published in Stem Cell Reports, October 2015 DOI: 10.1016/j.stemcr.2015.09.012.

Skin Cells Converted into Placenta-Generating Cells


Yosef Buganim and his colleagues from Hebrew University of Jerusalem have successfully reprogrammed skin fibroblasts in placenta-generating cells.

The placenta is a marvelously complex, but it is also a vital organ for the unborn baby. It supplies oxygen and nutrients to the growing baby and removes waste products from the baby’s blood. The placenta firmly attaches to the wall of the uterus and the umbilical cord arises from it.

The placenta forms from a population of cells in the blastocyst-stage embryo known as trophoblast cells. These flat, outer cells interact with the endometrial layer of the mother’s uterus to gradually form the placenta, which firmly anchors the embryo to the side of the uterus and produce a structure that serves as an embryonic kidney, endocrine gland, lung, gastrointestinal tract, immune system, and cardiovascular organ.

Trophoblast form after an embryonic event known as “compaction,” which occurs at about the 12-cell stage (around day 3). Compaction binds the cells of the embryo tightly together and distinguishes inner cells from outer cells. The outer cells will express the transcription factor Cdx2 and become trophoblast cells. The inner cells will express the transcription factor Oct4 (among others too), and will become the cells of the inner cell mass, which make the embryo proper.

Fetal growth restriction, which is also known as intrauterine growth restriction, refers to a condition in which a fetus is unable to achieve its genetically determined potential size. It occurs when gas exchange and nutrient delivery to the fetus are not sufficient to allow it to thrive in utero. Fetal growth restriction can lead to mild mental retardation or even fetal death. This disease also cause complications for the mother.

Modeling a disease like fetal growth restriction has proven to be very difficult largely because attempts to isolate and propagate trophoblast cells in culture have been unsuccessful. However, these new findings by Buganim and his colleagues may change that.

Buganim and his coworkers screened mouse embryos for genes that support the development of the placenta. They identified three genes – Gata3, Eomes, and Tfap2c – that, when transfected into skin fibroblasts, could drive the cells to differentiate into stable, fully-functional trophoblast cells. Buganim called these cells “induced trophoblast stem cells” or iTSCs.

In further tests, Hana Benchetrit in Buganim’s laboratory and her colleagues showed that these iTSCs could integrate into a developing placenta and contribute to it.

Buganim and his team are using the same technology to generate fully functional human placenta-generating cells.

If this project succeeds, it might give women who suffer from the curse of recurrent miscarriages or other placenta dysfunctions diseases the chance to have healthy babies. Also, since these iTSCs integrate into the placenta and not the embryo, they pose little risk to the developing baby.

This work was published in Cell Stem Cell 2015; DOI: 10.1016/j.stem.2015.08.006.

A Cell Delivery Methods that Uses Magnetic Fields


Injecting stem cells into the brain has serious risks. In the a case of patients who have experienced traumatic brain injury (TBI), intracranial injections of stem cells can cause intracranial hemorrhage. Also, the injected stem cells often fail to find their way to the injured parts of the brain. Therefore, you have a high-risk procedure that may yield few benefits.

However a new technique for getting stem cells into the brain has been designed and tested by Paul Yarowsky and his colleagues at the University of Maryland and the Veterans Administration Maryland Healthcare System.

Yarowsky and his coworkers labeled human neural progenitor cells with iron oxide “superparamagnetic nanoparticles” and directed team to the site of a brain injury by means of a magnetic field.

They tested this technique in rats that had suffered TBI and discovered that the delivery methods has no deleterious effects on the viability of the stem cells and not only increases stem cell homing to the site of injury, but also increased stem cell retention.

“Magnetic cell targeting is ideally suited to augmenting cell therapies. The external magnetic field and field gradient can guide cells to sites of injury and, using MRI, the iron-oxide superparamagnetic nanoparticles can be visualized as they travel to the site of injury. The goal when employing this method is not only guiding the particles to the site of injury, but also enhancing entry into the brain and the subsequent retention of the transplanted cells,” said Yarowsky.

The intensity of the magnetic field neither affects the viability of the cells in culture, nor their proliferation nor differentiation. This is also the case when the cells are loaded with iron oxide nanoparticles. These results suggest that this is indeed a promising technique for cell delivery in TBI patients and might also be useful for treating other neurological injuries and neurodegenerative diseases as well.

A critical question is, “what happens to the cells when the magnetic field is no longer present?”. Also, the patient must wear a magnetic hat in order to subject the cells to a magnetic field, but what is the minimum time the patient must wear it in order for the procedure to be successful?  All of these questions must be addressed to some degree if they this technique is to be properly understood. For now, Yarowsky and his colleagues assume that the optimized magnetic intensity observed in experiments with rodents must be extrapolated to larger animals, which may or may not be a legitimate extrapolation. Until larger animal experiments are conducted, this will remain a speculation.

Even though a good deal of work remains to be done, Yarowsky and his colleagues are still optimistic that their ingenious iron oxide nanoparticle procedure has promise and might, some day, be translated to human clinical trials.

This work was published in the journal Cell Transplantation, 21 September 2015.

Cord Blood Cells As a Potential Treatment for Alzheimer’s Disease


Jared Ehrhart from the University of South Florida, who also serves as the Director of Research and Development at Saneron CCEL Therapeutics Inc, and his coworkers have shown that cells from umbilical cord blood can not only improve the health of mice that have an experimental form of Alzheimer’s disease (AD), but these can also be administered intravenously, which is safer and easier than other more invasive procedures.

Laboratory mice can be engineered to harbor mutations that can cause a neurodegenerative disease that greatly resembles human AD. One such mouse is the PSAPP mouse that harbors two mutations that are known to cause an inherited, early-onset form of AD in humans. By placing both mutations in the same mouse, the animal forms the characteristic protein plaques more rapidly and shows significant AD symptoms and brain pathology.

Ehrhart used PSAPP mice to test the ability of human umbilical cord blood to ameliorate the symptoms of AD. He injected one million Human Umbilical Cord Blood Cells (HUCBCs) into the tail veins of PSAPP mice and 2.2 million into the tail veins of Sprague-Dawley rats. Then he harvested their tissues at 24 hours, 7 days, and 30 days after injection. Then Ehrhart and his team used a variety of techniques to detect the presence of the HUCBCs.

Interestingly, the HUCBCs were able to cross the blood-brain barrier and take up residence in the brain. The cells remained in the brain and survived there for up to 30 days and did not promote the growth of any tumors.

Several studies have shown that the administration of HUCBCs to mice with a laboratory form of AD can improve the cognitive abilities of those mice (see Darlington D, et al., Cell Transplant. 2015;24(11):2237-50; Banik A, et al., Behav Brain Res. 2015 Sep 15;291:46-59; Darlington D, et al., Stem Cells Dev. 2013 Feb 1;22(3):412-21). However, in such cases it is essential to establish that the administered cells actually found their way to the site of damage and exerted a regenerative response.

Even though Ehrhart and his troop found that the intravenously administered HUCBCs were widely distributed throughout the bodies of the animals, they persisted in the central nervous system for up to one month after they were injected. In the words of this publication, which appeared in Cell Transplantation, the HUCBCs were “broadly detected in both in the brain and several peripheral organs, including the liver, kidneys, and bone marrow.”. The fact that such a minimally invasive procedure like intravenous injection can effectively introduce these cells into the bodies of the PSAPP mice and still produce a significant therapeutic effect is a significant discovery.

Ehrhart and his colleagues concluded that HUCBCs might provide therapeutic effects by modulating the inflammation that tends to accompany the onset of AD. Furthermore, these cells do not need to be delivered by means of an invasive procedure like intracerebroventricular injection. Furthermore, even though HUCBCs were detected in other organs, their numbers in those places was not excessive and the ability of the HUCBCs to cross the blood-brain barrier suggests that these cells might serve as safe, effective therapeutic agents for AD patients some day.

Drugs that Increase Bone Marrow Stem Cell Mobilization Improves Heart Healing After a Heart Attack in Laboratory Mice


The laboratory of Ahmed Abdel-Latif at the University of Kentucky has used an acute heart attack model in laboratory mice to examine if fatty signaling molecules have the ability to improve the healing of the heart after a heart attack.

A host of studies have examined the ability of transplanted stem cells to help heal the heart after a heart attack. Many laboratories have examined the efficacy of stem cells from bone marrow (Afzal MR, et al., Circ Res. 2015 Aug 28;117(6):558-75), fat (Suzuki E, et al., World J Cardiol. 2015 Aug 26;7(8):454-65), and umbilical cord blood (Xing Y, et al., Cell Mol Biol (Noisy-le-grand). 2014 Jun 15;60(2):6-12) to improve heart function, prevent remodeling, help heart muscle cells survive, and promote the growth of new blood vessels. Unfortunately, while these studies have produced largely positive results, such stem cell treatments lack consistency in their activity and efficacy.

Heart attacks result from oxygen deprivation of the heart. The lack of oxygen causes heart muscle cells to die off. Heart muscle cells are not like skeletal muscle cells, which can work at an oxygen deficit. Instead, the oxygen-deprived heart muscle cells will die even after a show period of ischemia. This cell death causes the release of a host of molecules into the vicinity of the heart muscle that induces a sizable inflammatory response, which kills off even more cells. This inflammatory response, however, has a positive side too, since it can send signals to the rest of the body, in particular the bone marrow, and mobilize stem cells into the blood steam that eventually home to the damaged heart tissue. Once in the heart, these cells can mediate repair of the damaged heart (see Hsieh PC, et al., Nature Medicine 2007;13:970-974; Abdel-Latif A, et al., Exp Hematol 2010;38:1131-1142; Finan A and Richard S, Frontiers in Cell and Developmental Biology 2015; 3: 57).

The nature of the signals that bring bone marrow stem cells to the doorstep of the damaged heart have been the subject of some interest to several laboratories. Work from several different laboratories have shown that bone marrow stem cells are held in the bone marrow by means of a molecule called stromal-derived growth factor-1 (SDF-1), which is made by the bone marrow cells that surround the stem cell that binds to a receptor on the surface of the bone marrow stem cell called-CXCR4. This SDF-1/CXCR4 interaction keeps the bone marrow stem cell happy with its location. And additional binding between a stem cell surface protein called Very Late Antigen-4 (VLA-4; α4β1 integrin) and a receptor for VLA-4 called Vascular Adhesion Molecule-1 (VCAM-1; CD106), which is found on the surfaces bone marrow cells, tethers the bone marrow stem cells to the bone marrow and bone marrow niches (see Lapidot T, Dar A, Kollet O. Blood. 2005;106(6):1901–1910; Peled A, et al., J Clin Invest. 1999;104(9):1199–1211;Lévesque JP, et al., Blood. 2001;98(5):1289–1297; Lévesque JP, et al., J Clin Invest. 2003;111(2):187–196).

Bone marrow stem cells can be mobilized into the peripheral blood by infection, tissue injury, or after the administration of particular pharmacological agents such as granulocyte colony stimulating factor (G-CSF) or some polysaccharides such as Zymosan. Earlier thinking focused on the protein SDF-1, because several papers seemed to suggest a role for SDF-1 in stem cell recruitment of tissue repair after injury (Bobadilla M, et al., Stem Cells Dev. 2014 Jun 15;23(12):1417-27; Wen J, Am J Cardiovasc Dis. 2012;2(1):20-8; Yang JX, et al., J Biol Chem. 2015 Jan 23;290(4):1994-2006). However, SDF-1 does not seem to be the major signaling molecule that mobilizes bone marrow stem cells after a heart attack, because stem cell mobilization is not blocked if an antagonist for CXCR4 called AMD3100 is administered (See Ratajczak and others below). Instead, a group of lipids that are precursors for the synthesis of a group of membrane lipids known as “sphingolipids” seem to be the main signaling molecules for this event (see Ratajczak MZ, et al., Leukemia 2010;24:976-985).

sphingo

In particular, two molecules, sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) are probably the main players for this response. Thus, several stem cell scientists have predicted that giving people drugs that increase the concentrations of S1P and C1P might enhance healing of the heart after a heart attack through improved stem cell mobilization.

This is the point at which Ahmed Abdel-Latif and his colleagues com into the story, because Abdel-Latif’s lab used a drug called tetrahydroxybutylimidazole (THI) to do exactly that. THI inhibits an enzyme called S1P lyase (SPL), which degrades S1P. Therefore, THI raises the concentrations of S1p in the peripheral blood. Abdel-Latif and his coworkers administered THI to mice 4 days after they had suffered a heart attack. This time lag is essential because the first few days after the heart attack, the heart is a very hostile place, and any recruited or injected cells will die. However, 4 days is also well before scarring and scar formation occur in the heart.

Abdel-Latif and others observed that THI treatment lengthens the time period during which stem cells from the bone marrow are recruited and sent to the blood stream. The greater number of stem cells sent to the heart resulted in enhanced heart regeneration. The hearts of the THI-treated animals showed significantly better ejection fractions (average percentage of blood ejected from the ventricles per heart beat), increased heart wall thickness, and reductions in the size of the heart scar 5 weeks after their heart attacks.

When the mobilized bone marrow stem cells were isolated from peripheral blood and screened for gene expression, it was clear that these cells expressed a gaggle of stem cell homing, mobilization, cell survival, and blood vessel making genes. Thus, these mobilized stem cells were not only ready to go to the heart, but they were fully primed for to stimulate tissue healing.

Labeling studies also showed that bone marrow stem cells and progenitor cells flocked to the damaged hearts. The THI-treated mice had more than twice the number of labeled cells in their hearts at the edge of the infarct zone than the control animals 5 weeks after their heart attack. The THI-treated animals also showed significant increases in capillary densities in the THI-treated animals. As expected, there was no evidence that the mobilized bone marrow stem cells that differentiated into heart muscle cells. Thus, whatever benefits these cells convey to the heart is probably mostly by means of secreted exosomes, growth factors, and other mechanisms or so-called paracrine mechanisms.

This procedure worked rather well in laboratory mice. Can it work in human patients? That’s the $64,000 question. We have hints that increase bone marrow stem cells mobilization after a heart attack might improve recovery. However, this hint comes from a small clinical study in which levels of mobilized stem cells in the bloodstream after a cardiac event was correlated with clinical outcomes one year after the episode (Wyderka R, et al. Mediators Inflamm 2012;2012:564027). Such a study is at odds with studies that have pharmacologically mobilized stem cells from the bone marrow with intravenous G-CSF in patients after a heart attack with little benefit (Hilbert B, et al., CMAJ. 2014 Aug 5;186(11):E427-34; Archilli F., et al., Heart. 2014 Apr;100(7):574-81; Moazzami K, et al., Cochrane Database Syst Rev. 2013 May 31;5:CD008844. doi: 10.1002/14651858.CD008844.pub2). However, as noted in this paper, a drug called LX2931 is a THI analog and is already given as a treatment for rheumatoid arthritis, LX2931 is a safe drug and also inhibits SPL. Possibly future clinical trials that use either LX2931 or something akin to it will be tested in heart attack patients.

Gene Therapy for Stroke Applied with Eye Drops


Administering growth factors to the brains of patients with neurodegenerative diseases can prevent neurons from dying and maintain the structure of their brains. For example, a recently published clinical trial by Nagahara and others from the Department of Neuroscience and the University of California, San Diego examined 10 Alzheimer’s disease (AD) patients and showed that these patients responded to Nerve Growth Factor gene therapy. When they compared treated and nontreated sides of the brain in 3 patients who underwent gene transfer, expansion of cholinergic neurons was observed on the NGF-treated side. Both neurons exhibiting the typical pathology of AD and neurons free of such pathology expressed NGF, which indicates that degenerating cells can be infected with therapeutic genes. No adverse pathological effects related to NGF were observed. In the words of this study, “These findings indicate that neurons of the degenerating brain retain the ability to respond to growth factors with axonal sprouting, cell hypertrophy, and activation of functional markers. [Neuronal s]prouting induced by NGF persists for 10 years after gene transfer. Growth factor therapy appears safe over extended periods and merits continued testing as a means of treating neurodegenerative disorders.” See JAMA Neurol. 2015 Oct 1;72(10):1139-47.

Another study that also shows that the brains of AD patients can respond to growth factors comes from a paper by Ferreira and others from the Journal of Alzheimers Disease. These authors hail from the Karolinska Institutet, Stockholm, Sweden, and they implanted encapsulated NGF-delivery systems into the brains of AD patients. Six AD patients received the treatment during twelve months. These patients were classified as responders and non-responders according to their twelve-month change in the Mini-Mental State Examination (MMSE), which is a standard. In order to set a proper standard of MMSE decline and brain atrophy in AD patients, Ferreira and other examined 131 AD patients for longitudinal changes in MMSE and brain atrophy. When these results provided a baseline, the NGF-treated were then compared with these baseline data. Those patients who did not respond to the implanted NGF showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments than responding patients. The responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42, and less brain shrinkage and better progression in the clinical variables and CSF biomarkers. In particular, two responders showed less brain shrinkage than what was normally experienced in the baseline data. From these experiments, Ferreira and others concluded that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD.

Now new, even simpler treatment strategy has been developed by a research team funded by the National Institute of Biomedical Imaging and Bioengineering for delivering gene therapy to the brains of AD patients. This team invented an eye drop cocktail that can deliver the gene for a growth factor called granulocyte colony stimulating factor (G-CSF) to the brain. They have tested these eye drops on mice with stroke-like injuries.

When treated with these eye drops, the mice experienced a significant reduction in shrinkage of the brain, neurological defects, and death. Ingeniously, this research group also devised a way to use Magnetic Imaging Systems to monitor how well the gene delivery worked. This one-two punch of an inexpensive and noninvasive delivery system combined with a monitoring technique that is equally noninvasive might have the ability to improve gene therapy studies in laboratory animals. Such a strategy might also be transferable to human patients. Imagine that acute brain injury might be treatable in the near future by emergency medical workers by means of eye drops that carry a therapeutic gene.

The growth factor G-CSF (granulocyte-colony stimulating factor) has more than proven itself in several animal studies. In model systems for stroke, AD, and Parkinson’s disease, G-CSF promotes neuronal survival and decreases inflammation (See McCollum M, et al., Mol Neurobiol. 2010 Jun;41(2-3):410-9; Frank T, et al., Brain. 2012 Jun;135(Pt 6):1914-25; Prakash A, Medhi B, Chopra K. Pharmacol Biochem Behav. 2013 Sep;110:46-57; Theoret JK, et al., Eur J Neurosci. 2015 Oct 16. doi: 10.1111/ejn.13105). Unfortunately, when G-CSF was when tested in a human trial in more than 400 stroke patients, it failed to improve neurological outcomes in stroke patients. Therefore, it is fair to say that the excitement this growth factor once generated is not what is used to be. A caveat with this clinical trial, however, is that G-CSF expression in the brains of these patients might have been rather poor in comparison to the expression achieved in mice. To properly establish the efficacy or lack of efficacy of gene therapies in human patients, scientists MUST convincingly determine that the gene is expressed in the target tissue of test subjects. This has been a perennial problem that has dogged many gene therapy trials.

Philip K. Liu, Ph.D., of the Martinos Center for Biomedical Imaging at Harvard Medical School, and his collaborators, H. Prentice and J. Wu of Florida Atlantic University, developed the novel MRI-based techniques for monitoring G-CSF treatment and the eye drop-based delivery system as well. MRI can efficiently confirm successful administration and expression of G-CSF in the brain after gene therapy delivery. This work was published in the July issue of the journal Gene Therapy.

“This new, rapid, non-invasive administration and evaluation of gene therapy has the potential to be successfully translated to humans,” says Richard Conroy, Ph.D., Director of the NIBIB Division of Applied Science and Technology. “The use of MRI to specifically image and verify gene expression, now gives us a clearer picture of how effective the gene therapy is. The dramatic reduction in brain atrophy in mice, if verified in humans, could lead to highly effective emergency treatments for stroke and other diseases that often cause brain damage such as heart attack.”

Liu’s motivation for this project was to develop a gene delivery method that was simple, and could rapidly and effectively deliver the genes to the brain. A simple gene delivery technique would obviate the need for highly trained staff and expensive, sophisticated equipment. They also sought to successfully demonstrate the efficacy of their technology in laboratory animals so that it could be translated to humans.

To test their system, they deprived mice of blood flow to their brains, and then administered a genetically-engineered adenovirus that had the G-CSF gene inserted into its genome. This particular adenovirus is known to be quite safe in humans and can also efficiently infect brain cells. The adenovirus was also safely and effectively administered through eye drops. The simplicity of the eye drops means that it is easy to give multiple gene therapy treatments. By delivering the G-CSF gene at multiple time points after the induced blockage, Liu and others found that the treated mice showed significant reductions in deaths, brain atrophy, and neurological deficits as measured by behavioral testing of these mice.

MRI examinations also confirmed that G-CSF was expressed in treated mouse brains. Liu and his group used an MRI contrast agent tethered to a segment of DNA that targets the G-CSF gene. This inventive strategy enabled MRI imaging of G-CSF gene expression in mouse brains. The brains of mice treated with the recombinant adenovirus showed significant expression of the G-CSF gene. Control mice treated with the same adenovirus carrying the contrast agent bound to a different piece of DNA produced no MRI signal in the brain.

Control mice that did not receive G-CSF in eye drops, MRI scan identified areas of the brain with reduced metabolic activity and shrinkage as a result of the stroke. Mice treated with the G-CSF gene therapy, however, kept their usual levels of metabolic activity and did not have any evidence of brain atrophy. On average, after a stroke, mouse brain striatum size decreased more than 3-fold, from 15 square millimeters in normal mice to less than 5 square millimeters. But in contrast, G-CSF-treated mice retained an average striatum volume of more than 13 square millimeters, which is close to normal brain volume.

“We are very excited about the potential of this system for eventual use in the clinic,” says Liu, “The eye drop administration allows us to do additional treatments with ease when necessary. The MRI allows us to track gene expression and treatment success over time. The fact that both methods are non-invasive increases the ability to develop, and successfully test gene therapy treatments in humans.”

Liu and his collaborators are now jumping through the multitudes of hoops to take this work to a clinical trial. They are trying to secure FDA approval for the use of the G-CSF gene therapy in human patients. Finally, they also need to invite collaborating with physicians to develop their clinical trial protocol.

3D Printing of Stem Cells on Bioceramic Molds to Reconstruct Skulls


Skull defects or injuries can be very difficult to repair. However, an Australian research team has pioneered a new technique that can regrow skulls by applying stem cells to a premade scaffold with a 3D printer.

This research team consists of a surgeon, a neurosurgeon, two engineers, and a chief scientist. This five-person team is collaborating with a 3D printing firm that is based in Vienna in order to manufacture exact replicas of bone taken from the skulls of patients.

The protocol for this procedure utilizes stem cells and 3D printers, and is funded by a $1.5 million research grant that is aimed at reducing costs and improving efficiency of the Australian public health service.

The first subjects for this procedure will include patients whose skulls were severely damaged, or had a piece of their skull removed for brain surgery, and require cranial reconstruction. The skull reconstructions will take place at the Royal Perth Hospital. The first trial will commence next year. If this procedure proves to be successful it could reduce the risk of complications and surgical time, and provide massive cost savings.

If a patient has a skull injury or some other skull issue, pieces of skull bone were removed bone and stored it in a freezer for later implantation into the skull. Unfortunately, this procedure often resulted in infection or resorption of the bone. Alternatively, titanium plates can be used but these eventually they degrade, and therefore, are not ideal.

Neurosurgeon Marc Coughlan, who is a member of the five-person research team that developed this procedure, said this protocol represents the first time stem cells have been used on a 3D printed scaffold to regrow bone. “What we’re trying to do is take it one step further and have the ceramic resorb and then be only left with the patient’s bone, which would be exactly the same as having the skull back,” Coughlan told The Australian.

If this procedure proves successful, it could revolutionize cranial reconstruction surgeries. According to health minister Kim Hames, “This project highlights some of the innovative and groundbreaking research that is under way in WA’s public health system, and the commitment of the government to supporting this crucial work.”

We will keep tabs on this clinical trial to determine if it works as well as reported.