Delivery of a Missing Protein Heals Damaged Hearts in Animals

Stanford University School of Medicine scientists have enabled the regeneration of damaged heart tissue in animals by delivering a protein to it by means of a bioengineered collagen patch.

“This finding opens the door to a completely revolutionary treatment,” said Pilar Ruiz-Lozano, PhD, associate professor of pediatrics at Stanford. “There is currently no effective treatment to reverse the scarring in the heart after heart attacks.”

Ruiz-Lozano and her colleagues published their data online in the journal Nature.

During a heart attack, cardiac muscle cells or cardiomyocytes die from a lack of blood flow. Replacing dead cells is vital for the organ to fully recover, but, unfortunately, the adult mammalian heart does not possess a great deal of regenerative ability. Therefore, scar tissue forms instead of heart muscle, and since scar tissue does not contract, it compromises the ability of the heart to function properly.

Heart attacks kill millions of people every year, and the number of heart attacks is predicted to rise precipitously in the next few decades. The number of heart attacks might even triple by 2030. Approximately, 735,000 Americans suffer a heart attack each year, and even though many victims survive the initial injury, the resulting loss of cardiomyocytes can lead to heart failure and even death. “Consequently, most survivors face a long and progressive course of heart failure, with poor quality of life and very high medical costs,” Ruiz-Lozano said. Transplanting healthy muscle cells and stem cells into a damaged heart have been tried, but these trials have mixed results, typically, and have yet to produce consistent success in promoting healing of the heart.

Previous heart regeneration studies in zebrafish have shown that the outer layers of the heart, known as the epicardium, is one of the driving tissues for healing a damaged heart. Ruiz-Lozano said, “We wanted to know what in the epicardium stimulates the myocardium, the muscle of the heart, to regenerate.” Since adult mammalian hearts do not regenerate effectively, Ruiz-Lozano and her co-workers wanted to know whether epicardial substances might stimulate regeneration in mammalian hearts and restore function after a heart attack.

She and her colleagues focused on Fstl1, which is a protein secreted by the epicardium, and acts as a growth factor for cardiomyocytes. Not only did this protein kick-start the proliferation of cardiomyocytes in petri dishes, but Ruiz-Lozano and others found that it was missing from damaged epicardial tissue following heart attacks in humans.

Next, Ruiz-Lozano and her colleagues reintroduced Fstl1 back into the damaged epicardial tissue of mice and pigs that had suffered a heart attack. They embedded a bioengineered patch on to the damaged heart tissue that was imbued with Fstl1. Then they sutured the patch, loaded with Fstl1, to the damaged tissue. These patches were made of natural material known as collagen that had been structurally modified to mimic certain mechanical properties of the epicardium.

Because the patches are made of collagen, they contain no cells, which mean that recipients do not need immunosuppressive drugs to avoid rejection. With time, the collagen material is absorbed into the heart. The elasticity of the material resembles that of the fetal heart, and seems to be one of the keys to providing a hospitable environment for muscle regrowth. New blood vessels regenerated there as well.

Within two to four weeks of receiving the patch, heart muscle cells began to proliferate and the animals progressively recovered heart function. “Many were so sick prior to getting the patch that they would have been candidates for heart transplantation,” Ruiz-Lozano said. The hope is that a similar procedure could eventually be used in human heart-attack patients who suffer severe heart damage.

The work integrated the efforts of multiple labs around the world, including labs at the Sanford-Burnham-Prebys Medical Discovery Institute in San Diego, UC-San Diego, Boston University School of Medicine, Imperial College London and Shanghai Institutes for Biological Sciences.

Stanford has a patent on the patch, and Ruiz-Lozano is chief scientific officer at Epikabio Inc., which has an exclusive option to license this technology.

Stem Cell Treatments to Repair Cartilage Defects in the Knee

Erosions of the cartilage that covers the surfaces at the ends of our leg bones has motivated several laboratories to undertake clinical studies to test new techniques to heal lost cartilage, particularly at the knee. Many of these techniques have their share of drawbacks and advantages, but the number of clinical trials to deal with cartilage lesions of the knee are increasing. Unfortunately, more work remains to be done, but much more is known about several of these techniques than before. This article will summarize many of these techniques.

Microfracture is a procedure in which several small holes are drilled into the end of the bone to enhance the migration of mesenchymal stem cells from the bone marrow to the site of the cartilage defect. These MSCs then differentiate into chondrocytes and make cartilage that fills the lesion with new cartilage. Unfortunately, the cartilage made in these cases is fibrocartilage and not hyaline cartilage. Fibrocartilage lacks the biomechanical strength and durability of hyaline cartilage and it typically deteriorates 18-24 months after surgery. When used to treat large lesions, 20-50% of all cases develop intralesional osteophytes and the sclerotic bone increases the failure rate of autologous chrondrocyte implantation 3-7X. Thus microfractionation is only performed under very specific conditions and only in young patients, since this technique does not work in older patients.


Autologous Chondrocyte Implantation or ACI uses a full-thickness punch biopsy from a low-weight-bearing region of the joint taken during an arthroscopic surgery. This biopsy contains chondrocytes that are grown in cell culture to a population of about 12-48 million chondrocytes, which are troweled into the lesion during a second arthroscopic surgery. Clinical trials have established that ACI is safe and effective for large knee lesions. Peterson and others and Minas and others have established that even after 10 years, patients who have been treated with ACI show good relief of pain and increased knee function.

In the Peterson study, questionnaires were sent to 341 patients. 224 of 341 patients replied to the questionnaires, and of these respondents, 74% of the patients reported their status as better or the same as the previous years 10-20 years after the procedure (mean, 12.8 years).  92% were satisfied and would have ACI again.  Knee function and pain levels were significantly better after the procedure than before.  From this study, Peterson and others concluded that ACI is an effective and durable solution for the treatment of large full-thickness cartilage and osteochondral lesions of the knee-joint, and that the clinical and functional outcomes remain high even 10 to 20 years after the implantation.

Minas and others analyzed data from 210 patients treated with ACI who were followed for more than 10 years. ACI provided durable outcomes with a survivorship of 71% at 10 years and improved function in 75% of patients with symptomatic cartilage defects of the knee at a minimum of 10 years after surgery. A history of prior marrow stimulation as well as the treatment of very large defects was associated with an increased risk of failure.
In comparison studies by Bentley and others, ACI produced superior results to mosaicplasty (osteochondral transplantation or cylinders of bone drilled form low-weight-bearing parts of the knee that are implanted in a mosaic fashion into the knee).  In the Bentley study, 10 of 58 ACI patients had failed grafts after 10 years, but 23 of 42 mosaicplasty patients had failed cartilage repair.  According to studies by Based and others, and Saris and others, ACI is also superior to microfractionation in the repair of large cartilage lesions (>3 cubic cm), but seems to provide the same outcomes as microfracture for smaller lesions, according to Knudsen and others.  There are drawbacks to ACI.  The tissue flap used to seal the cartilage implant sometimes becomes pathologically enlarged.  Other materials have been used to seal the patch, such as hyaluronic acid, or collagen types I and III, but the use of these materials increases the expense of the procedure and the likelihood that the immune system will response to the covering.  Also, ACI outcomes vary to such an extent that the procedure is simply too unstandardized at the present time to be used consistently in the clinic.

Autologous Cartilage Implantation

In an attempt to standardize ACI, several orthopedic surgeons have tried to add a supportive scaffold of some sort to the chondrocytes harvested from the patient’s body.  Several studies in tissue culture have shown that chondrocytes not only divide better, but also keep their identities as chondrocytes better in a three-dimensional matrix (see Grigolo et al, Biomaterials (2002) 23: 1187-1195 and Caron et al, Osteoarthritis Cartilage (2012) 20; 1170-1178).  Therefore, ACI has given way to MACI or Matrix-Induced Autologous Chondrocyte Implantation, which seeds the chondrocytes on an absorbable porcine-derived mixed collagen (type I and III) prior to implantation.  The implant is then secured into the debrided cartilage lesion by means of a fibrin cover.

Several case studies have shown that MACI has substantial promise, but individual case studies are the weakest evidence available.  To prove its superiority over ACI or microfracture surgery, MACI must be compared in controlled studies.  In the few studies that have been conducted, the superiority of MACI remains unproven to date.  Patients who received MACI or ACI showed similar clinical outcomes in two studies (Bartlett and others, Journal of Bone and Joint Surgery (2005) 87: 640-645; and Zeifang et al, American Journal of Sports Medicine (2010) 38: 924-933), although those who received MACI showed a significantly lower tendency for the graft to enlarge.  MACI is clearly superior to microfracture surgery (Basad, et al., Knee Surgery, Sports Traumatology and Arthroscopy (2010) 18: 519-527), but longer-term studies are needed to establish the superiority of MACI over other treatment options.

A slight variation of the MACI theme is to embed the chondrocytes in a gel-like material called hyaluronic acid (HA).  HA-embedded chondrocytes have been shown to promote the formation of hyaline cartilage in patients (Maracci et al., Clinical Orthopedics and Related Research (2005) 435: 96-105).  Even though the outcomes are superior for patients treated with HA-MACI, the recovery period is longer (Kon E, et al., American Journal of Sports Science (2011) 39: 2549-2567).  MACI is available in Europe but not the US to date.  FDA approval is supposedly pending.  Long-term follow-up studies are required to establish the efficacy of this procedure.

Future prospects for treating knee cartilage lesions include culturing collagen-seeded chondrocytes for a longer period of time than the three days normally used for MACI.  During these longer culture periods, the seeded chondrocytes mature, and make their own scaffolds, which ensure higher-quality cartilage and better chondrocyte engraftment (see Khan IM and others, European Cell Materials (2008) 16: 26-39).  Alternatively, joint cartilage responds to stress by undergoing cell proliferating and increasing in density.  This response is due to the production of growth factors such as Transforming Growth Factor-β1 and -β3 (TGF-β1 and TGF-β3).  This motivated some enterprising tissue engineers to use recombinant forms of these growth factors to grow cartilage in bioreactors under high-stress conditions.  Such a strategy has given rise to NeoCart, a tissue-engineered product that has gone through Phase I and II trials and has been shown in two-year follow-up studies to be safe and more effective than microfracture surgery (Crawford DC and others, Journal of Bone and Joint Surgery, American Volume. 2012 Jun 6;94(11):979-89 and Crawford DC, and others, Am J Sports Med. 2009 Jul;37(7):1334-43).

Mesenchymal stem cells (MSCs) from bone marrow and other sites have also been used to successfully treat cartilage lesions.  These types of treatments are less expensive than ACI and MACI, and do not require two surgeries as do ACI and MACI.  The studies that have been published using a patient’s own MSCs have been largely positive, although some pain associated with the site of the bone marrow aspiration is a minor side effect (see Centeno and others, Pain Physician (2008) 11:343-353; Emadedin, et al., Arch Iran Med (2012) 15: 422-428; Wong RL, et al., Arthroscopy (2013) 29: 2020-2028).  Fat-based MSCs have been tested as potential cartilage-healers in elderly patients (Koh YG, et al., Knee Surgery, Sports Traumatology, and Arthroscopy (Dec 2013, published on-line ahead of print date).  While these initial results look promising,, fat-based, MSCs have only just begun to be tested for their ability to regenerate cartilage.  Fat-based MSCs show different properties than their bone-marrow counterparts, and it is by no means guaranteed that fat-based MSCs can regenerate cartilage as well as MSCs from bone marrow.

Fresh cartilage grafts from donors (aka – cartilage allografts) use transplanted cartilage that has been freshly collected from a donor.  Fresh cartilage allografts have had positive benefits for young, active patients and the grafts have lasted 1-25 years (Gross AE, et al., Clinical Orthopedics and Related Research (2008) 466: 1863-1870).  Particulate cartilage allografts takes minced cartilage and lightly digests it with enzymes to liberate some of the cartilage-synthesizing chondrocytes, and then pats this material into the cartilage lesion, where it is secured with a fibrin glue plug.  The cartilage provides an excellent matrix for the synthesis of new cartilage, and the chondrocytes make new cartilage while seeded onto this cartilage scaffold.  Clinical experience with this technique includes a two-year follow-up in which MRI evidence showed good filling of the lesions (Bonner KF, Daner W, and Yao JQ, Journal of Knee Surgery 2010 23: 109-114 and Farr J, et al., Journal of Knee Surgery 2012 25: 23-29).  A variation on this technique uses a harvested hyaline cartilage plug that is glued into an absorbable scaffold before transplantation into the cartilage lesion.  This procedure had the same safety profile as microfracture surgery, but resulted in better clinical outcomes, high quality cartilage, and fewer adverse side effects (Cole JB et al., American Journal of Sports Medicine 2011 39: 1170-1179).  A clinical trial that tested this procedure remains uncompleted after the company suspended the trial because of conflicts with the FDA (Clinical Trial NCT00881023).

AMIC or Autologous Matrix-Induced Chondrogenesis is a cell-free treatment option in which the cartilage lesion is cleaned and filled subjected to microfracture, after which the lesion is filled with a mixed collagen matrix that is glued or stitched to the cartilage lesion.  The MSCs released by the microfracture procedure now move into a scaffold-laden cartilage lesion that induces the formation of hyaline cartilage.  This technique appears to aid the filling of full-thickness cartilage defects, and follow-up examinations have revealed that after 5 years, patients showed substantial improvements in knee function, pain relief and MRI analyses of knee cartilage showed high-quality cartilage in repaired lesion (Kusano T, et al., Knee Surgery, Sports Traumatology, and Arthroscopy 2012 20: 2109-2115; Gille J, et al., Archives of Orthopedic Trauma Surgery 2013 133: 87-93; Gille J, et al., Knee Surgery, Sports Traumatology, and Arthroscopy 2010 18: 1456-1464).

These are just a few of the new treatments of cartilage lesions of the knee and other joints.  As you can see, all of this will lead to greater repair of knee lesions and it is all being done without embryonic stem cells or destroying embryos.

Mesenchymal Stem Cells Make Tendons on Fabricated Collagen

Ozan Akkus and his colleagues from the Department of Mechanical and Aerospace Engineering at Case Western Reserve University in Cleveland, Ohio has succeeded in making fibers made completely from the protein collagen. Why is this a big deal? Because it is so bloody hard to do.

In a paper published the journal Advanced Functional Materials, Akkus and others describe the generation of their three-dimensional collagen threads. This is the first time anyone has described the formation of such threads made purely from collagen.

Collagen is a very widely distributed protein in our bodies. It is the major structural component of tendons, and most connective tissues, and as a whole, collagen composes approximately one-third of all the protein in our bodies. There are almost 30 different types of collagen; some collagens for stiff fibers and others form flat networks that act as cushions upon which cells and other tissues can sit.

Collagen biosynthesis is very complicated and occurs in several steps. First, the collagen genes are transcribed into messenger RNAs that are translated by ribosomes into collagen protein. However, collagen proteins are made in a longer, inactive form that must undergo several types of modifications before it is usable.

Collagen synthesis begins in a compartment of the cell known as the endoplasmic reticulum, which is a series of folded membranes associated with the nuclear membrane. Within the endoplasmic reticulum, the end piece of the collagen protein, known as the signal peptide, is removed by enzymes called signal peptidases that clip such caps off proteins. Now particular amino acids within the collagen protein chains are chemically modified. The significance of these modifications will become clear later, but two amino acids, lysine and proline, and -OH or hydroxyl groups added to them. This process is called “hydroxylation,” and vitamin C is an important co-factor for this reaction. Some of the hydroxylysine residues have sugars attached to them, and three collagen protein chains now self-associate to form a “triple ɣ helical structure.” This “procollagen” as it is called, is shipped to another compartment in the cell known as the Golgi apparatus. Within the Golgi apparatus, the procollagen it is prepared to be secreted to the cell exterior. Once secreted, collagen modification continues. Other proteins of the collagen protein chains called “registration peptides” are clipped off by procollagen peptidase to form “tropocollagen.” Multiple tropocollagen molecules are then lashed together by means of the enzyme lysyl oxidase, which links hydroxylysine and lysine residues together in order to form the collagen fibrils. Multiple collagen fibrils form a proper collagen fiber. Variations on a theme are also available, since collagen can also, alternatively, attached to cell membranes by means of several types of proteins, including fibronectin and integrin.


Now, if the cells has to go through all that just to make a collagen fiber, how tough do you think it is to make collagen fiber in a culture dish? Answer – way hard. In order to make collagen threads, Akkus and his team had to use a novel method for mature collagen production, and then they compacted the collagen molecules by means of the mobility of these molecules in an electrical field. This “electrophoretic compaction” method also served to properly align the collagen molecules until they formed proper collagen threads. Biomechanical analyses of these fabricated collagen threads showed that they had the mechanical properties of a genuine tendon. Akkus’ group when one step further and showed that a device they designed with movable electrodes could fabricate continuous collagen threads (). Thus, Akkus and his crew showed that they could make as many collagen threads as they needed and that these threads worked like tendons (see here for video). Are these guys good or what?

A. Schematic of basic electro-chemical cell layout for collagen alignment; B. Polarized image confirming the alignment of ELAC; C. Human mesenchymal stem cells on ELAC threads at day 1 and day 14. Cell form a confluent layer on day 14. Scale bar: 0.5 mm.
A. Schematic of basic electro-chemical cell layout for collagen alignment; B. Polarized image confirming the alignment of ELAC; C. Human mesenchymal stem cells on ELAC threads at day 1 and day 14. Cell form a confluent layer on day 14. Scale bar: 0.5 mm.

Nest, Akkus and his gang seeded collagen threads with mesenchymal stem cells (MSCs) from bone marrow. Remarkably, these collagen thread-grown mesenchymal stem cells differentiated into tenocytes, which are the cells that made tendons. Normally, MSCs do not readily form tenocytes in the laboratory, and they do not easily make tendons. However, in this case, the MSCs not only differentiated into tenocytes and made tenocyte-specific proteins and genes, but they do so without the addition of exogenous growth factors; the collagen threads were all the cells needed.

The seeded MSCs made Collagen I, which is the most abundant collagen of the human body, and is present in scar tissue, tendons, skin, artery walls, corneas, the endomysium surrounding muscle fibers, fibrocartilage, and the organic part of bones and teeth. Other tendon-specific proteins that were made included tenomodulin, and COMP (Cartilage oligomeric matrix protein). Furthermore, the electrically-aligned collagen does a better job of inducing the tenocyte fate in MSCs than collagen that is randomly oriented.

These remarkable and fascinating results demonstrate scaffolds made of densely compacted collagen threads stimulates tendon formation by Mesenchymal stem cells. Thus electrically aligned collagen as a very promising candidate for functional repair of injured tendons and ligaments. Now it is time to show that this can work in a living creature. Let the preclinical trials commence!!

Sweat Glands Are A Source of Stem Cells for Wound Healing

Stem Cells from human sweat glands serve as a remarkable source for wound healing treatments according to a laboratory in Lübeck, Germany.

Professor Charli Kruse, who serves as the head of the Fraunhofer Research Institute for Marine Biotechnology EMB, Lübeck, Germany, and his colleagues isolated cultured pancreatic cells in the course of their research to look into the function of a protein called Vigilin. When the pancreatic cells were grown in culture, they produced, in addition to other pancreatic cells, nerve and muscle cells. Thus the pancreas contains a stem cell population that can differentiate into different cell types.

Kruse and his group decided to investigate other glands contained a similar stem cell population that could differentiate into other cell types.

Kruse explained: “We worked our way outward from the internal organs until we got to the skin and the sweat glands. Again, this yielded the same result: a Petri dish full of stem cells.”

Up to this point, sweat glands have not received much attention from researchers. Mice and rats only have sweat glands on their paws, which makes them rather inaccessible. Human beings, on the other hand, have up to three million sweat glands, predominantly on the soles of out feet, palms of the hand, armpits, and forehead.

Ideally, a patient could have stem cells taken from her own body to heal an injury, wound, or burn, Getting to these endogenous stem cell populations, however, represents a challenge, since it requires bone marrow biopsies or aspirations, liposuction, or some other invasive procedure.

Sweat glands, however, are significantly easier to find, and a short inpatient visit to your dermatologist that extracts three millimeters of underarm skin could provide enough stem cells to grow in culture for treatments.

Stem cells from sweat glands have the capacity to aid wound healing. Kruse and his group used sweat gland-based stem cells in laboratory animals. The Kruse group used skin biopsies from human volunteers and separated out the sweat gland tissues under a dissecting scope. Then the sweat gland stem cells were grown in culture and induced to differentiate into a whole host of distinct cell types.

Then Kruse’s team grew these sweat gland stem cells in a skin-like substrate that were applied to wounds on the backs of laboratory animals. Those animals that had received stem cell applications healed faster than those that received no stem cells.

If the stem cells were applied to the mice with the artificial substrate, the cells moved into the bloodstream and migrated away from the site of the injury. In order to help heal the wound the cells had to integrate into the skin and participate in the healing process.

“Not only are stem cells from sweat glands easy to cultivate, they are extremely versatile, too,” said Kruse.

Kruse and his team are already in the process of testing a treatment for macular degeneration using sweat gland-based stem cells. “In the long-term, we could possibly set up a cell bank for young people to store stem cells from their own sweat glands/ They would then be available for use should the person need new cells, following an illness,l perhaps, or in the event of an accident,” Kruse said.

Rejuvenating Aged Stem Cells With a Fountain-Of-Youth Cocktail

Stem cell researchers from the laboratory of Ren-Ke Li at the University of Toronto have discovered a cocktail that can kick old, lagging stem cells in the backside and renew their regenerative capacities.

Donated bone marrow stem cells are transplanted into patients with leukemia, or diseases that compromise bone marrow function. Unfortunately, even though such therapies save hundreds to thousands of lives every year, some of these patients die or become horribly ill because the patient rejects some of the cells in the donated bone marrow. To reduce the risk of bone marrow rejection, stem cells treatments have used stem cells from the patient’s own body. Unfortunately, such a strategy is unusable in older patients, since their stem cell function has been vitiated by the ravages of age. If there is a way to beef up the stem cell function of an older patient, why then, this protocol would definitely be preferred.

Ren-Ke Li, professor in the Division of Cardiovascular Surgery and a member of the Institute for Biomaterials and Biomedical Engineering at the University of Toronto, Canada and his colleague Milica Radisic, an associate professor of chemical engineering have designed a unique micro-environment that allows heart tissue to grow from stem cells donated by elderly patients.

This micro-environment utilizes a porous scaffold made of collagen (the protein found in scar tissue), and embedded in this scaffold are two growth factors (vascular endothelial growth factor and basic fibroblast growth factor). Radisic and Li and their co-worked seeded these scaffolds with stem cells taken from younger (~50 years old) and older donors (~75 years old) and then used them to repair the left ventricles of rats with damaged hearts.

The scaffolds without growth factors and seeded with stem cells from older donors did not repair the hearts very well, but those scaffolds without growth factors and seeded with stem cells from younger donors did a good job of repairing the hearts. When the scaffolds impregnated with growth factors were seeded with stem cells from older donors, the patches did a much better job of repairing the hearts; they did as good a job of facilitating heart repair and those scaffolds seeded with stem cells from younger patients.

Patch Morphology 28 Days After Implantation In Vivo(A) Representative images of rat hearts show the outer border of the patches depicted by the yellow dotted line. (B) Patch area was quantified using computerized planimetry. The patch area increased in all groups from the original size of 39 mm2(red dotted line) at the time of SVR. Patch area in the Old group was significantly larger after implantation than that in the other groups. The addition of cytokines significantly prevented patch expansion. (C) Representative images of heart slices stained with Masson's trichrome. Arrows indicate patch thickness. (D) Patch thickness was quantified using computerized planimetry. The patches in the Old group were significantly thinner than patches in the Young and Young + GF groups. Cytokine enhancement did not significantly increase patch thickness for old or young cells. *p < 0.05, **p < 0.01 vs. Old; Old n = 5, Young n = 8, Old + GF n = 6, Young + GF n = 8. GF = growth factor.
Patch Morphology 28 Days After Implantation In Vivo(A) Representative images of rat hearts show the outer border of the patches depicted by the yellow dotted line. (B) Patch area was quantified using computerized planimetry. The patch area increased in all groups from the original size of 39 mm2(red dotted line) at the time of SVR. Patch area in the Old group was significantly larger after implantation than that in the other groups. The addition of cytokines significantly prevented patch expansion. (C) Representative images of heart slices stained with Masson’s trichrome. Arrows indicate patch thickness. (D) Patch thickness was quantified using computerized planimetry. The patches in the Old group were significantly thinner than patches in the Young and Young + GF groups. Cytokine enhancement did not significantly increase patch thickness for old or young cells. *p < 0.05, **p < 0.01 vs. Old; Old n = 5, Young n = 8, Old + GF n = 6, Young + GF n = 8. GF = growth factor.

When Li and his team tracked the molecular changes in the stem cells grown on the scaffolds, they found that these cells acted like younger stem cells. In Li’ words: “We saw certain aging factors turned off.” The levels of two molecules in particular, p16 and RGN were reduced in the older stem cells grown on the growth factor-containing scaffolds, which turned back the clock in these cells and returned them to a more robust and healthy state.

Li and Radisic hope to experiment with their micro-environment in order to make it as effective as possible. According to Li, “We can create much better tissues which can then be used to repair defects such as aneurysms.” Li also thinks that these cells could be used to repair the heart after a heart attack.

See Kai Kang, et al., Aged Human Cells Rejuvenated by Cytokine Enhancement of Biomaterials for Surgical Ventricular Restoration,” Journal of the American College of Cardiology 2012 60(21): 2237 DOI: 10.1016/j.jacc.2012.08.985.