Wrongful Birth Lawsuit

According to the publication New Scientist, estimates by the Israeli medical profession postulate that there have been at least 600 ‘wrongful life’ lawsuits since the first case in 1987. A ‘wrongful life’ lawsuit occurs when the parents of a child with some kind of developmental abnormality or genetic disease sue the doctors who helped birth the child in the name of the child. The lawsuits allege that had the parents known about fetus’ severe genetic problem, they would have chosen to terminate their pregnancy.

“Wrongful life” claims are generally brought by the children, or much more typically, parents acting on behalf of the children.  Essentially, the lawsuit specifies that the children are suing for the right to have never been born.  They are suing doctors for NOT putting them to death. According to an article in BioNews, the psychological implications of such lawsuits on the children named in them have been noted by several medical ethicists.  Professor Rabbi Avraham Steinberg of University Hadassah Medical School, Jerusalem, commented: “I find it very difficult to understand how parents can go on the witness stand and tell their children ‘it would have better for you not to have been born. What are the psychological effects on the children?”

Now in the state of Oregon, a “wrongful life” lawsuit in Portland was put forward involving a Down syndrome child. According to the newspaper, the Oregonian, in June 2007, Ariel and Deborah Levy were excited by the birth of their daughter, when then experienced profound shock and anger when hospital staff told them their daughter had Down syndrome.  When asked if she had had a prenatal test in the form of a chorionic sampling test, Mrs. Levy answered in the affirmative.  Unfortunately, the results showed that they were going to have a normal, healthy child.  Several days after being born, a blood test confirmed that the Levy’s little girl, Kalanit Levy, had Down syndrome.  Therefore, the Levys filed suit against legacy Health, claiming that they would have aborted the pregnancy if they had known that their daughter had Down syndrome.  The Levys say that they “dearly love their daughter, who is now 4 years old, but they want Legacy to pay for the extra life-time costs of caring for her, which are estimated to be about $3 million.

With all respect to the Levys, but this, “We dearly love her but would have killed her before she was born” schtick does not wash.  What if she learns that her parents brought this case.  Doctors cannot guarantee outcomes.  We do not have a right to a particular child and no one should have to be legally declared wrongfully born.  If the jury has any sense in this matter, they will throw this case out.  It is a clear-cut case of chasing deep pockets with a detestable premise.

Different Kinds of Stem Cells in the Heart

For almost a century, the sciences of human physiology, cardiology, and medicine have believed that the heart is a terminally differentiated organ whose cells do not undergo further cell division. Essentially however many heart cells you were born with persisted throughout your own personal lifespan. Any increases in the size of the heart were thought to result from expansion of the size of the heart muscle cells .

Work from several labs over the last 15 years have shown that this dogma does not stand further scrutiny. In 1995, Peiro Anversa and his colleagues at New York Medical College in Valhalla, NY examined the differences in heart size between men and women at various ages and found that heart mass was stable in women, but in men, loss of heart mass was due to cell loss and not a decrease in cell size. Also, cell size was stable in women, but tended to increase in men. This increase in cell volume compensated for the loss of heart muscle cells and kept the thickness of the heart walls the same in older and younger men. However, the mass of the heart still decreased in men as they age. This finding does not support the assumption that heart muscle cells are born during development and stay with you throughout your life (for this study see Giorgio Olivetti, et al., Gender Differences and Aging: Effects on the Human Heart. JACC Vol. 26, No. 4 (1995): 1068-79).

Other work that contradicted the commonly accepted dogma examined hearts of people who had experienced “acromegalic cardiomyopathy.”  In a nutshell, individuals with acromegalic cardiomyopathy had a problem with too much growth hormone.  This growth hormone imbalance caused the patient to be really tall, and suffer from bone abnormalities.  This also causes enlargement of the heart.  This patient died at the age of 65, and had a heart that weighed 800 grams.  This is six times the weight of a normal heart.  However, when the size of the heart muscle cells from the man who had died of acromegaly were compared with that of a 99-year old women who had died of pneumonia, the volume of their cells was similar (Leri, Kajstura and Anversa, Role of Cardiac Stem Cells in Cardiac Pathophysiology: A Paradigm SHift in Human Myocardial Biology. Circulation Research 109 (2011): 941-61).  This strongly calls into question the notion that heart enlargement is due to an increase in cell size.

Why was the acromegalic heart larger?  The answer seems to be that it contained far more cells, and recent work has demonstrated that hearts have a stem cell population that can divide and generate new heart cells.  At all ages, the heart contains heart muscle cells that are dividing and expressing a host of genes found only in dividing cells (CDC6, Ki67, MCM5, Phospho-H3, aurora B kinase).  When the heart enlarges for pathological reasons, the proportion of heart muscle cells that expresses these genes increases (see Levi P, Kajstura J and Anversa P, Cardiac Stem Cells and Mechanisms of Myocardial Regeneration. Physio Rev 85 (2005): 1373-1416).

There is not one population of heart stem cells, but four of them, and they all possess different characteristics, and, possibly, different embryological origins.  The first group is “side population cells.”  Side population cells (SPCs) are identified by their ability to expel toxic compounds and dyes (Hierlihy AM, Seale P, Lobe CG, Rudnicki MA, Megeney LA. The post-natal heart contains a myocardial stem cell population. FEBS Lett.2002 Oct 23;530(1-3):239-43).  SPCs have a membrane protein that pumps such molecules from the cell, and when cultured in a semisolid medium, they will differentiate into heart muscle cells.  The exact genes expressed by SPCs is uncertain, since there seem to be, at least in rodents, a few subclasses of SPCs.  In mice, 2% of all heart cells are SPCs, and they have an expression pattern that looks like this: Sca1[high], c-kit[low], CD34[low], and CD45[low].  Cells that express Sca1 normally form blood vessels, but SPCs do not seem to form blood vessels.  This is the conclusion of cell tracing experiments that marks cells and then places them into damaged hearts.  Once the stem cells have divided and integrated into the heart, the animals are sacrificed and their hearts are stained for the marker that characteristic of the implanted stem cells.  Such experiments show that SPCs do not make blood vessels in mice (Tara L. Rasmussen, et al., Getting to the Heart of Myocardial Stem Cells and Cell Therapy. Circulation. 2011; 123: 1771-1779).

In rats, the data is less clearly interpretable, because rat SPCs express a gene called Bcpr1, but the Bcpr1-positive cells either express CD31 and can form blood vessels or do not express CD31 and cannot form blood vessels.  It appears that only the Sca-1[positive] CD31[negative] cells have a pronounced ability to form heart muscle cells.  SCPs might come from neural crest cells, and this hypothesis comes from their behavior in culture (Oyama et al., Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo.  J Cell Biol 176 (2007): 329-41).

The second population of cardiac stem cells is the Sca-1 cells.  Sca1 cells do not possess the functional properties of stem cells, but they represent 2% of all heart cells.  While they can be grown in culture, only a very small percentage of the cells express any heart muscle-specific proteins (3%-4%), and when delivered to a damaged heart, Sca1 cells will fuse with existing cells to modestly improve heart function (Matsuura K., et al., JBC 279 (2004): 11384-91).  When injected into damaged hearts, Sca1 cells form blood vessels but their ability to survive in the heart is very poor (Li Z., et al., JACC 53 (2009): 1229-40).  Also, Sca1 cells seem to secrete molecules that help the heart and its other stem cell populations to work better.  Most of the heart muscle turnover seems to result from c-kit[positive] cells and the role of SPCs and Sca1 cells is, to date, uncertain.

On the cardiac surface, a third heart stem cells exists, the epicardial progenitors.  There are several different subtypes of epicardial progenitors; Flk1-expressing cells form blood vessels, WT1- and Tbx18-expressing cells make heart muscle (Zhou B., et al., Nature 454 (2008): 109-13 and Cai CL., et al., Nature 454 (2008): 104-108).  There is also a pool of c-kit[positive] cells in the human heart that can differentiate into heart muscle cells and blood vessels (Castaldo C, et al., Stem Cells 26(7), 2008: 1723-31).

The final heart stem cell population is the cardiosphere derived cell (CDC) population.  “Cardiospheres” are balls of cells formed by CDCs in culture.  While in these spheres, a variety of cells form around a core of primitive, c-kit[positive] cells.  Cardiospheres do not consist of a uniform mass of cells, but a pastiche of cells.  Some of these cells have gap junction proteins that are found in mature heart muscle cells that allow them to connect with each other and pass ions from one cell to another.  Others are highly uncommitted and have tremendous growth potential.  These cells express c-kit at high levels.  CDCs are the stem cells that have been used in the recent CADUCEUS and SCIPIO clinical trials.  They are capable of forming heart muscle cells and blood vessels.  They are also easily extracted from hearts by biopsies that are out-patient procedures.

Thus even though there are several different types of heart stem cells, they play a role in repair, and pathology.  They can also be exploited to heal hearts, shrink heart scars, and make a denser collection of blood vessels in the heart.  Further work on them will increase the ability of cardiologists to heal the hearts of patients with failing hearts.

Induced Pluripotent Stem Cell Treatments for Heart Attacks

Several recent papers have used induced pluripotent stem cells (iPSCs) to treat heart attacks in laboratory animals. These papers followed similar strategies that included culturing iPSCs, differentiating those iPSCs into heart muscle cells, surgically inducing a heart attack in laboratory rodents, and then transplanting the iPSC-induced heart muscle cells into the hearts of the animals that suffered a heart attack. The results are beyond encouraging; they are remarkable.

The first paper is from James Thomson’s laboratory at the University of Wisconsin, Madison (Zhang J, et al., Circ Res. 2009 Feb 27;104(4):e30-41). In this paper, human iPSCs were differentiated into heart muscle cells. These heart muscle cells expressed many heart muscle-specific genes and proteins, and also had mixed characteristics. Some of the cells resembled heart muscle from the upper part of the heat (atrial), some looked like heart muscle from the lower part of the heart (ventricular), and still others had similarities to heart pacemaker cells. These iPSC-derived heart muscle cells also showed the same response to heart medicines that normal, native heart muscle would show. Thus human iPSCs can form functional heart muscle cells.

While experiment paralleled experiments with mouse iPSCs (see Mauritz C, et al., Circulation. 2008 Jul 29;118(5):507-17; & So KH, et al., Int J Cardiol. 2011 Dec 15;153(3):277-85), it begged the question: “Could these iPSC-derived heart muscle cells integrate into a working heart and act like normal heart muscle cells?” These answer to this question in a certifiable “Yes!”

The first paper – Mauritz C., et al., Eur Heart J. 2011 Nov;32(21):2634-41; examined mouse iPSCs and their ability to differentiate into heart muscle cells that could be used to treat laboratory animals with heart attacks.  These workers from Kutschka’s lab found that iPSC-derived heart muscle came in two forms; those that expressed an enzyme called “fetal liver kinase-1” and those that did not.  Fetal liver kinase-1 or Flk-1 is a receptor for a growth hormone called vascular endothelial growth factor (VEGF).  VEGF is a major stimulator of blood vessel formation, and Flk-1 confers upon cells the ability to respond to VEGF and form blood vessels.

Kutschka’s lab workers isolated the Flk-1-positive cells from the Flk-1-negative cells by means of a cell sorter, but they did not other extremely important experiment.  They used cells that expressed a fluorescent protein if and only if they had not completely differentiated.  This way, all incompletely differentiated cells were removed by the cell sorter.  Since incompletely differentiated iPSCs can cause tumors, this is an important safety consideration if this technology is ever to see the light of clinical trials.  The two heart muscle cell populations were then implanted into the hearts of laboratory mice that had suffered heart attacks.  Control mice were injected with saline.

The results showed that both populations of iPSC-derived heart muscle cells integrated into the injured hearts and increased heart function and structure.  However the Flk-1-positive cells conferred even more benefits onto the hearts.  Furthermore, because these iPSC-derived heart muscle cells were produced from adult cells that came from the animals that had suffered heart attacks, there was no need to use mice that had defective immune systems, or were given immunosuppressive drugs.  This definitely shows that iPSC-based treatments are ready for human clinical trials at some time in the near future.

The second paper – Singla DK, et al., Mol Pharm. 2011 Oct 3;8(5):1573-81; takes a slightly different approach.  This research group from the University of Central Florida made iPSCs from a cultured heart muscle cell line called H9c2.  Singla and colleagues transfected these cells with four genes (Oct3/4, Sox2, Klf4, and c-Myc) and this successfully transformed the cultured heart muscle cells into iPSCs.  Then they differentiated those iPSCs into heart muscle cells that beat in culture and also expressed essential heart muscle proteins.  When transplanted into the hearts of laboratory animals that had recently suffered a heart attack, these iPSC-derived muscle cells made proper contacts with other heart muscle cells, properly communicated with them, and improved heart function much better than transplantation of H9c2 cells, or those injected with no cells.  Once again, we have the same strain of mouse from which H9c2 was made.  These mice did not require any suppression of the immune system to receive this treatment because they received cells made from their own genetic stock, and the immune system recognized them as part of themselves.

Finally, a paper by Nelson TJ, et al., Circulation. 2009 Aug 4;120(5):408-16 – from the Mayo Clinic in Rochester, Minnesota also shows the feasibility of iPSCs for regenerative therapy in laboratory animals.  In this paper, undifferentiated iPSCs were transplanted into the hearts of laboratory rodents that had recently suffered heart attacks.  The iPSCs were placed into differentiation media and transplanted into the hearts of mice with poorly operating immune systems and those with normal immune systems.  In the mice with poorly functional immune systems, the implanted iPSCs formed aggressive tumors that overtook the heart and eventually killed the animal.  However, in those animals with normally-operating immune systems, no tumors formed, and the iPSCs form heart-specific cell types and properly engrafted into the heart without disrupting te structure of the heart.  iPSC treatment also regenerated cardiac, smooth muscle, and endothelial tissue, and restored post-heart attack function when it came to contractile performance, the thickness of the ventricular wall, and the electrophysiology of the heart.

These experiments show that iPSCs can fix injured hearts.  There are even protocols to safely differentiate them into heart muscle cells.  Clearly the safety of these must be better investigated and established before they can transition to clinical trials.  However, these papers are definitely a good start to what will hopefully become, some day, personalized stem cells to treat an ailing heart.

Hydrogen Sulfide Induces Dental Pulp Stem Cells to Become Liver Cells

The gas hydrogen sulfide smells like rotten eggs, and it is also poisonous in high quantities. It is produced throughout the body, and the exact role of it is unknown. However, scientists from the Nippon Dental University in the laboratory of Ken Yaegaki have shown that small quantities of this gas can induce particular adult stem cells to differentiate into liver cells.

Human teeth contain several stem cell populations, and one of these, the dental pulp stem cells, can make liver cells with remarkable efficiency. Dental pulp is composed of connective tissue and cells and dental pulp stem cells can be obtained from teeth after extraction.

Human tooth pulp stem cells contain a subpopulation that possesses a particular cell surface molecule called “CD117,” which is also known as the mast/stem cell growth factor receptor.  Those cells with this surface protein were isolated from the rest of the stem cells.  They then grew these stem cells in culture, and transferred them to a culture medium that contained a basic nutrient medium (Dulbecco’s modified Eagle’s medium for those who might be interested) and added to that medium, insulin, an iron-binding protein called transferrin, and two growth factors (embryotrophic factor and hepatocyte growth factor) for five days. Then they transferred the cells to another medium that was similar to the previous medium, but also had a cytokine called “oncostatin” and a steroid drug called dexamethasone for 15 days.  The atmosphere for these cells included either 5% carbon dioxide, and no or a small amount of hydrogen sulfide (0.05 ng ml−1).

After growing cells under these conditions, those cells that had been grown in the presence of hydrogen sulfide were more liver-like when it came to their biochemistry.  Liver cells store large amounts of sugar in the form of glycogen, produce a waste product called urea as a result of a pathway called the urea cycle, and make a large cadre of enzymes and proteins that are specific to the liver.  In almost every case, the cells grown in the presence of hydrogen sulfide made more liver-specific proteins than those grown without hydrogen sulfide.  The production of urea and glycogen were also increased, and glycogen storage was about five times greater in the hydrogen sulfide-treated group than in the control.  especially glycogen which was approximately five times greater compared to the control (p < 0.01). As a result of these experiments, the research group concluded that physiological concentrations of hydrogen sulfide increase the ability of human tooth pulp stem cells to undergo differentiation into liver cells.

Yaegaki commented, “Until now, nobody has produced the protocol to regenerate such a large number of hepatic (liver) cells for human transplantations.  Compared to the traditional method of using fetal bovine serum to produce the cells, our method is productive and, most importantly, safe.”  Yaegaki continued: “Moreover, these facts suggest that patients undergoing transplantation with the hepatic cells may have no possibility of developing teratomas or cancers, as can be the case when using bone marrow stem cells.”

Clearly, dental stem cells are from a tissue that is normally thrown out.  This new life for exfoliated teeth might provide a new role for these tooth-bound stem cells, and might also provide a new way to treat those with devastating liver diseases.  For example, systemic lupus erythematosis can decimate the patient’s liver, and without a transplant, the patient might die.  Adaptation of this protocol might drive other adult stem cell populations to produce liver cells for therapeutic purposes.  The potential is certainly great.

High Blood Pressure Medicine Improves Mesenchymal Stem Cell Treatments of Heart Attacks

Mesenchymal stem cells (MSCs) exist in a variety of places throughout the body. They are found in bone marrow, the lower levels of the skin, umbilical cord and umbilical cord blood, placenta, amniotic membrane, muscle, blood vessels, liver, synovial membranes that surround joints, endometrial glands, fat, tendons, and other locations as well. MSCs have the ability to differentiate into cartilage-making cells, fat-making cells, muscle-making cells or bone-making cells  Other protocols exist to differentiate MSCs into heart muscle (Williams AR, Hare JM. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease.Circ Res. 2011 Sep 30;109(8):923-40; Song YH, Pinkernell K, Alt E.Stem cell induced cardiac regeneration: fusion/mitochondrial exchange and/or transdifferentiation? Cell Cycle. 2011 Jul 15;10(14):2281-6.), neurons (Scuteri A, Miloso M, Foudah D, Orciani M, Cavaletti G, Tredici G.Mesenchymal stem cells neuronal differentiation ability: a real perspective for nervous system repair? Curr Stem Cell Res Ther. 2011 Jun;6(2):82-92), and liver cells (Al Battah F, De Kock J, Vanhaecke T, Rogiers V. Current status of human adipose-derived stem cells: differentiation into hepatocyte-like cells. ScientificWorldJournal. 2011;11:1568-81).  The therapeutic possibilities of MSCs has been widely recognized by stem cell scientists and MSCs have been the subject of many past and ongoing clinical trials.

The use of MSCs to treat heart attack patients has been the subject of several clinical trials (Mazo M, Araña M, Pelacho B, Prosper F. Mesenchymal stem cells and cardiovascular disease: a bench to bedside roadmap. Stem Cells Int. 2012;2012:175979).  While MSCs do provide a modicum of healing to damaged hearts, the ability of MSCs to differentiate into heart muscle is low.  Many experiments have focused upon increasing the percentage of implanted MSCs  that differentiate into heart muscle cells.  However, a recent paper from a research group at the Keio University School of Medicine and the National Institute for Child Health and Development in Tokyo, Japan has taken a different approach to this problem.

Drugs that treat blood pressure include the “angiotensin II receptor blockers” or ARBs.  ARBs prevent a small polypeptide called angiotensin II from binding its receptor.  WHen it binds to its receptor, angiotensin II causes rather substantial constriction of blood vessels throughout the body, and this raises blood pressure.  By preventing blood vessel constriction, ARBs can lower blood pressure.  Also, many heart attack patients are on blood pressure medicines, and ARBs are one of the those normally given to heart attack patients.

One particular ARB is called candesartan, and the commercial names are Atacand, Amias, Blopress, and Ratacand.  In this paper by Yohei Namasawa and colleagues in the laboratories of Kaoru Segawa, Satoshi Ogawa, and Akihiro Umezawa, determined if treating human MSCs from bone marrow could increase the ability of these cells to form heart muscle cells.  To induce heart muscle cells, they used a popular technique from the literature that grows MSCs in culture with mouse heart muscle cells.  The interaction between the MSCs and the heart muscle cells in culture drives the MSCs to form heart muscle-like cells at a somewhat low-frequency.  This group determined if MSCs became heart muscle cells by testing for the presence of heart muscle-specific proteins (cardiac-specific troponin-I).  To prevent them from confusing MSCs with the mouse heart muscle cells, the MSCs were pre-labeled with a fluorescent protein.

Candesartan treatment of MSCs more than doubled the ability of MSCs to form heart muscle cells in culture.  When these same cells were transplanted into the hearts of rats that had suffered heart attacks, the results were even more interesting.  MSC transplantation into the hearts of rats that had recently suffered a heart attack.  Those animals that had undergone surgery but were not given any heart attacks, showed an average reduction of about 3% in their ejection fraction (percentage of blood that pumped from the heart during each heart beat).  Given that the standard deviation was close to this number, this change is not significant.  The control animals that were not given MSC treatments showed an average decrease of just over 10% in their ejection fraction.  Animals treated with MSCs that had suffered heart attacks showed a decrease of about 6-7%.  This is significantly less of a decrease than in the control, but it is still a decrease.  When the rat hearts were treated with MSCs that had been pretreated with candesartan, they showed an average 3-4% increase in ejection fraction.  If the rats were given candesartan after the heart attack, it raised the ejection fraction 1-2%.  If the rats were given candesartan, and treated with bone marrow cells after the heart attack, their ejection fractions decreased by the same as the sham group.  However, if the rats were given candesartan and MSCs that had been pretreated with candesartan after the heart attack, their ejection fractions increased by 10-12%.  Other heart function indicators improved too, since transplantation of the candesartan-treated bone marrow cells improved the “end systolic dimension,” which is an indication of how well the heart contracts.

When hearts were examined after the animals died, those animals that had received transplantations of the candesartan-pretreated bone marrow cells had 2-3 times more heart muscle cells derived from the implanted MSCs than did the controls transplanted with non-treated bone marrow.  Also, post-mortem examination of hearts from the treated rats showed that the rats treated with candesartan-pretreated bone marrow cells had much small heart scars than the other groups (5%-7% smaller).

These experiments, though pre-clinical, suggest that pre-treatment of MSCs with compounds like candesartan can increase their ability to differentiate into heart muscle cells.  This would certainly augment their ability of heal the hearts of patients after a heart attack.  While further work is certainly warranted, a clinical study should be proposed to test if this efficacy applies to human hearts as well.

Induced Pluripotent Stem Cells Form Red Blood Cells

Concerns over the mutations that occur when adult cells are reprogrammed into induced pluripotent stem cells has caused scientists to step back and take a second look at this technology. Can such a technology be used to treat human patients safely?

Some cells in our bodies lack nuclei. For example, platelets and red blood cells do not have nuclei, and therefore, they lack a human genome. If red blood cells can be made from pluripotent stem cells, they could potentially treat patients who suffer from anemia. The red blood cells will not harbor any mutations because they do not have DNA. Thus, induced pluripotent stem cells could potentially be used to treat patients.

A paper in Stem Cells and Development by Jessica Dias and colleagues in the laboratory of Igor Slukvin at the University of Wisconsin, Madison has reported the generation of red blood cells from human induced pluripotent stem cells (J. Dias, et al., Stem Cells and Dev 20, no 9 (2011): 1639-47).

To make red blood cells from induced pluripotent stem cells (iPSCs), they made human iPSCs from skin cells called “fibroblasts” that were taken from new-born babies.  They made they iPSCs with methods that did not use viruses.  Instead they placed in the fibroblasts, small circles of DNA that contained all the genes necessary to create iPSCs.  These small circles of DNA are called “episomes.” and they can create iPSCs without maintaining themselves in the cells.  That is to say, once the episomes convert the adult cells into iPSCs, they are lost and do contaminate the genome of the iPSCs.

After making iPSCs, they grew them for seven days with two other cells; human embryonic stem cells and a mouse bone marrow cell line called OP9.  This combination converted the iPSCs into bone marrow stem cells.  The bone marrow stem cells were isolated and cultured for five days with chemicals that are known to push bone marrow stem cells to become red blood cells.  These chemicals (erythropoietin, stem cell factor, thrombopoietin, interleukin-3, dexamethasone, insulin, interleukin-6, and iron), drove the stem cells to become red blood cell-like cells.  Because these cells were also grown under conditions that prevented them from attaching they grew and differentiated.  After five days, the cells were maintained on another mouse bone marrow cells line called MS5 cells.

Dias and her colleagues also used an alternative technique that worked just as well that did not include isolating the bone marrow stem cells, but subjected the cells to a Percoll centrifugation that also isolated the differentiating cells from the other cells.  This technique seemed faster and less troublesome.

Neither of these techniques could be employed if these cells were to be used for human treatments.  The use of animal cells lines could contaminate the iPSCs with animal viruses or animal proteins.  Both of these would cause the human immune system to react adversely to the cells (Martin MJ, Muotri A, Gage F, Varki A. Human embryonic stem cells express an immunogenic nonhuman sialic acid.Nat Med. 2005 Feb;11(2):228-32).  Therefore, some other protocol will need to be devised if this type of treatment is employed for anemic humans.

Nevertheless, this culture did generate red blood cells that expressed mainly embryonic and fetal types of hemoglobin.  While there was some adult hemoglobin made, it was the minority molecule.  All of the cells produced by this cell culture system were of the same type as those that produce red blood cells (erythroid), and not of those that make white blood cells (myeloid).  This shows that it is feasible to make red blood cells from iPSCs, and it might even be feasible to produce them in a culture system that makes large quantities of them.  Other uses for culture systems like this could include making red blood cells to grow malarial parasites for drug research.  Clearly this is a remarkable discovery that may lead to a source of red blood cells for patients and laboratories alike.