Freethought & Rationalism Archive

Wounded King · 04-11-2003, 02:57 AM

Hey there,

OK so we know that ES cells are truly totipotent, but how vital is that? There is a lot of research showing that specific populations of multipotent adult progenitor cells (MAPCs) can develop into a wide variety of tissues. I am fully convinced of the need for ES research to determine the differing potentialities of ES and MAPC based systems of in vitro organ production, but I am not convinced that ES cells will neccessarily prove to be that superior. This is due to the obvious problems of immunoreactivity in organs grown from non self ES cells. The obvious answer to this is to use cloned ES cells of course, but this simply adds yet another layer of technical difficulty to the producing of an in vitro grown, non immunogenic, organ. By the time we have the technology to properly culture complex whole organs in vitro Im not convinced there will be a compelling rationale to use ES cells cloned or otherwise.

Would anyone care to comment on these views? I can add some references if anyone is interested.

Godot · 04-11-2003, 07:56 AM

I think the benefits of stem cell research far ouweigh any potential issues against it. I for one would be interested in your references, your highness.

ps418 · 04-11-2003, 08:32 AM

My opinion is that there are no compelling moral arguments against the use of ES cells, so to me the choice should be merely an issue of technical convenience. As long as some researchers would like to use them and some donors would like to donate them, they should be used.

Patrick

Wounded King · 04-11-2003, 11:49 AM

Here then are a few references, I have include some pro and con papers, and a few opinion pieces. These are just references, not links.

Pro:

Weimann JM, Charlton CA, Brazelton TR, Hackman RC, Blau HM.
Contribution of transplanted bone marrow cells to Purkinje neurons in human
adult brains.
Proc Natl Acad Sci U S A 2003 Feb 18;100(4):2088-93

Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, Crain B.
Transplanted bone marrow generates new neurons in human brains.
Proc Natl Acad Sci U S A 2003 Feb 4;100(3):1364-9

Bonilla S, Alarcon P, Villaverde R, Aparicio P, Silva A, Martinez S.
Haematopoietic progenitor cells from adult bone marrow differentiate into cells that express oligodendroglial antigens in the neonatal mouse brain.
Eur J Neurosci 2002 Feb;15(3):575-82

Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM.
Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain.
Exp Hematol 2002 Aug;30(8):896-904

Deb A, Wang S, Skelding KA, Miller D, Simper D, Caplice NM.
Bone marrow-derived cardiomyocytes are present in adult human heart: A study of gender-mismatched bone marrow transplantation patients.
Circulation 2003 Mar 11;107(9):1247-9

Con:-

Wagers AJ, Sherwood RI, Christensen JL, Weissman IL.
Little evidence for developmental plasticity of adult hematopoietic stem cells.
Science 2002 Sep 27;297(5590) p.p.2256-9

Morshead CM, Benveniste P, Iscove NN, van der Kooy D.
Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations.
Nat Med 2002 Mar;8(3):268-73

Opinion pieces (mixed):-

Clarke D, Frisen J.
Differentiation potential of adult stem cells.
Curr Opin Genet Dev 2001 Oct;11(5):575-80

Vogel G.
Stem cell policy. Can adult stem cells suffice?
Science 2001 Jun 8;292(5523):1820-2

I'm sorry to say that I have not read all these papers, I have read those that I have access to, such as the PNAS ones, but in some cases I have had to make do with the abstracts, in true undergraduate essay tradition.

I certainly feel there is no strong moral grounds for not proceeding with either ES or human ES cloning research. I simply feel that there is too strong a bias towards embryonic stem cell research to the detriment of other possible avenues, this is probably exacerbated by the pressure from so many quarters to have all stem cell research banned.

I may not feel that ES research is the last best hope for a number of diseases, as it is sometimes portrayed, but I would certainly defend the scientists right to research it, not neccessarily to the death I'm afraid, we all have our limits.

ps418 · 04-23-2003, 10:21 AM

A new source of stem cells has been announced -- the pulp of 'baby teeth.' Other than nerve and dentin cells, Its not yet known what types of cells these stem cells can differentiate into. Contrary to what the press release below suggest, the paper does not seem to have been published yet.

Scientists discover unique source of stem cells

In other stem cell news, a paper published in the American Heart Association's journal, Circulation, reports a signficant improvement of heart function following 15 small intracardial injections of bone-marrow derived stem cells. The injections were accomplished using a new device called a NOGA catheter, which allows researchers to pinpoint the desired injection site within the heart. The baseline ejection fraction (the fraction of total blood ejected per heartbeat) in the treated group increased from 20% to 29%, which means that the patients are still suffering from severe heart failure. Normal EF is 50% or higher. But who knows how much room for improvement there may be? Its still very good news.

Stem cells improve heart function of seriously ill heart failure patients

Perrin et al, 2003. Transendocardial, Autologous Bone Marrow Cell Transplantation for Severe, Chronic Ischemic Heart Failure. Circulation Published online before print April 21, 2003.

Patrick

Majestyk · 04-23-2003, 11:53 AM

Quote:

Originally posted by Wounded King
but I am not convinced that ES cells will neccessarily prove to be that superior.

They may prove to be inferior. At that point we won't really need them, but that has yet to be proven.

abe smith · 04-24-2003, 06:21 AM

the likelihood may be that "It's Not Quite Time Yet" to assert an answer; because we haven't adequate data yet.
Waiting-to-know-enough is always hard! and/but that may be the only intelligent action to (not) take.

ps418 · 04-28-2003, 06:53 AM

More stem cell news:

Wang et al (2003) have clarified the mechanisms whereby bone-marrow (haematopoietic) stem cells rescue liver function in mice with fumarylacetoacetate hydrolase deficiency. As it turns out, it is not by the differentiation of haematopoietic stem cells into liver cells. Rather, it appears that the stem cells fuse with liver cells (hepatocytes). A paper in the same issue of Nature by Vassilopoulos et al (2003) clarifies the the mechanism underlying the fusion-associated rescue of hepatocyte function in these mice. They show that following fusion with recipient hepatocytes, the donor haematopoietic stem cells "adopts a more hepatocyte-specific expression profile after cell fusion, as the wild-type Fah gene was activated and the pan-haematopoietic CD45 marker was no longer expressed."

And on a related note, Rambhatla et al (2003) report successfully inducing human embryonic stem (hES - as opposed to bone marrow stem cells) cells to differentiate into hepatocytes or hepatocyte-like cells following treatment of Hes with sodium butyrate. "The differentiated cells have morphological features similar to that of primary hepatocytes and 70-80% of the cells express liver-associated proteins (albumin, alpha-1-antitrypsin, cytokeratin 8 and 18), accumulate glycogen, have inducible cytochrome P450 activity, and do not express alpha-fetoprotein. Because of the inherent proliferative capacity of hES cells, these cells may provide a reliable source of normal human hepatocytes for research and transplantation."

In an article in the latest issue of the journal Cell Transplantation, it is demonstrated in mice that adult haematopoietic stem cells can differentiate into nerve cells.

Quote:

Adult stem cells were injected into a mouse blastocyst, an early embryonic stage of a mouse. The result is the birth of a chimerical animal an animal that shows the presence of both the cells from the host mouse as well as cells that have developed from the transplanted stem cells. Within the brain, the transplanted stem cells developed into nerve cells that typically conduct electrical impulses, glial cells that provide support to the nerve cells, and myelin-forming cells that enhance the conduction of electrical impulses by nerve cells.

�This research takes our findings a step further,� said principal investigator Walter C. Low, Ph.D., department of Neurosurgery, University of Minnesota Medical School.

Researchers looked at the specific phenotypes of the cells in the brain and found stem cell produced nerve cells in regions of the brain that undergo degeneration with Parkinson�s disease, multiple sclerosis, Huntington�s disease, ataxia, and Alzheimer�s disease.

�This tells us that these adult stem cells are capable of becoming nerve cells that communicate with other nerve cells within the brain and form proper neural circuits that permit the chimerical mice to function normally,� said co-investigator Catherine Verfaillie, M.D., director of the Stem Cell Institute at the University of Minnesota.

Press Release

More is being learned about a protein, called WNT, that regulates the proliferation of stem cells. In Nature Advanced Online Publications, Willert et al (2003) report isolating the protein for the first time, while Reya et al (2003) show that WNT expression regulates the proliferation of haematopoietic stem cells. Understanding the role of WNT obviously will be useful for all kinds of stem cell research. For instance, it may show how to induce massive profileration of stem cells in vitro or in vivo without inducing differentiation.

Refs

Rambhatla et al, Generation of hepatocyte-like cells From human embryonic stem cells. Cell Transplantation 12, 1-11 (2003).

Reya et al, A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature AOP, published online 27 April 2003.

Wang et al, Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422, 897 - 901 (2003).

Vassilopoulos et al, Transplanted bone marrow regenerates liver by cell fusion. Nature 422, 901 - 904 (2003).

Willert et al, Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature AOP, published online 27 April 2003.

Patrick

Wounded King · 04-28-2003, 07:12 AM

The fact that WNT regulates embryonic stem cell proliferation in haematopoetic populations is supremely unsurprising. Id imagine that a number of FGFs, BMPs and all the other usual supects of the developmental biology world will perform the same sort of tasks in ES populations as they do in the developing embryo.

Austin TW, Solar GP, Ziegler FC, Liem L, Matthews W.
A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells.
Blood. 1997 May 15;89(10):3624-35.

Van Den Berg DJ, Sharma AK, Bruno E, Hoffman R.
Role of members of the Wnt gene family in human hematopoiesis.
Blood. 1998 Nov 1;92(9):3189-202.

Lako M, Lindsay S, Lincoln J, Cairns PM, Armstrong L, Hole N.
Characterisation of Wnt gene expression during the differentiation of murine embryonic stem cells in vitro:role of Wnt3 in enhancing haematopoietic differentiation.
Mech Dev. 2001 May;103(1-2):49-59.

ps418 · 05-02-2003, 05:31 AM

Stil more stem cell news.

In an article published online at Science, Hubner et al (2003) report inducing mouse ES cells to diferentiate into oocytes and then into blastocysts:

Quote:

Continuation of the species requires the formation and development of the sexually dimorphic germ cells. Cultured embryonic stem cells are generally considered pluripotent rather than totipotent due to the failure to detect germline cells under differentiating conditions. Here we show that mouse embryonic stem cells in culture can develop into oogonia that enter meiosis and recruit adjacent cells to form follicle-like structures and later develop into blastocysts. Oogenesis in culture should contribute to various areas including nuclear transfer, manipulation of the germline, and advance studies on fertility treatment and germ and somatic cell interaction and differentiation.

Hubner et al, Derivation of Oocytes from Mouse Embryonic Stem Cells. Science, Published online May 1, 2003.

From the press release:

Quote:

PHILADELPHIA -- Researchers at the University of Pennsylvania have created the first mammalian gametes grown in vitro directly from embryonic stem cells. The work, in which mouse stem cells placed in Petri dishes -- without any special growth or transcription factors -- grew into oocytes and then into embryos, will be reported this week on the web site of the journal Science.

The results demonstrate that even outside the body embryonic stem cells remain totipotent, or capable of generating any of the body's tissues, said lead researcher Hans R. Sch�ler of Penn's School of Veterinary Medicine.

"Most scientists have thought it impossible to grow gametes from stem cells outside the body, since earlier efforts have yielded only somatic cells," said Sch�ler, professor of reproduction medicine and director of Penn's Center for Animal Transgenesis and Germ Cell Research. "We found that not only can mouse embryonic stem cells produce oocytes, but that these oocytes can then enter meiosis, recruit adjacent cells to form structures similar to the follicles that surround and nurture natural mouse eggs, and develop into embryos."

Sch�ler said oocyte development in vitro may offer a new way for embryonic stem cells to be produced artificially, sidestepping the ethical concerns articulated by President Bush and others. Implanting a regular nucleus from any of the body's cells into such an oocyte would yield a totipotent stem cell.

Press Release

Commentary in Nature Science Update

Gametes and embryos from mammalian stem cells: religious and ethics perspectives

Patrick

04-11-2003, 02:57 AM	#1
Wounded King Veteran Member Join Date: Mar 2003 Location: Edinburgh Posts: 1,211	Do we really need embryonic stem cells? Hey there, OK so we know that ES cells are truly totipotent, but how vital is that? There is a lot of research showing that specific populations of multipotent adult progenitor cells (MAPCs) can develop into a wide variety of tissues. I am fully convinced of the need for ES research to determine the differing potentialities of ES and MAPC based systems of in vitro organ production, but I am not convinced that ES cells will neccessarily prove to be that superior. This is due to the obvious problems of immunoreactivity in organs grown from non self ES cells. The obvious answer to this is to use cloned ES cells of course, but this simply adds yet another layer of technical difficulty to the producing of an in vitro grown, non immunogenic, organ. By the time we have the technology to properly culture complex whole organs in vitro Im not convinced there will be a compelling rationale to use ES cells cloned or otherwise. Would anyone care to comment on these views? I can add some references if anyone is interested.

04-24-2003, 06:21 AM	#7
abe smith Veteran Member Join Date: Apr 2001 Location: springfield, MA. USA Posts: 2,482	As w/ many other similar qq, the likelihood may be that "It's Not Quite Time Yet" to assert an answer; because we haven't adequate data yet. Waiting-to-know-enough is always hard! and/but that may be the only intelligent action to (not) take.

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04-11-2003, 07:56 AM	#2
Godot Veteran Member Join Date: Mar 2003 Location: Calgary Posts: 1,335	I think the benefits of stem cell research far ouweigh any potential issues against it. I for one would be interested in your references, your highness.

04-11-2003, 08:32 AM	#3
ps418 Veteran Member Join Date: Mar 2001 Location: Louisville, KY, USA Posts: 1,840	My opinion is that there are no compelling moral arguments against the use of ES cells, so to me the choice should be merely an issue of technical convenience. As long as some researchers would like to use them and some donors would like to donate them, they should be used. Patrick

04-11-2003, 11:49 AM	#4
Wounded King Veteran Member Join Date: Mar 2003 Location: Edinburgh Posts: 1,211	Here then are a few references, I have include some pro and con papers, and a few opinion pieces. These are just references, not links. Pro: Weimann JM, Charlton CA, Brazelton TR, Hackman RC, Blau HM. Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains. Proc Natl Acad Sci U S A 2003 Feb 18;100(4):2088-93 Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, Crain B. Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci U S A 2003 Feb 4;100(3):1364-9 Bonilla S, Alarcon P, Villaverde R, Aparicio P, Silva A, Martinez S. Haematopoietic progenitor cells from adult bone marrow differentiate into cells that express oligodendroglial antigens in the neonatal mouse brain. Eur J Neurosci 2002 Feb;15(3):575-82 Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM. Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol 2002 Aug;30(8):896-904 Deb A, Wang S, Skelding KA, Miller D, Simper D, Caplice NM. Bone marrow-derived cardiomyocytes are present in adult human heart: A study of gender-mismatched bone marrow transplantation patients. Circulation 2003 Mar 11;107(9):1247-9 Con:- Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002 Sep 27;297(5590) p.p.2256-9 Morshead CM, Benveniste P, Iscove NN, van der Kooy D. Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations. Nat Med 2002 Mar;8(3):268-73 Opinion pieces (mixed):- Clarke D, Frisen J. Differentiation potential of adult stem cells. Curr Opin Genet Dev 2001 Oct;11(5):575-80 Vogel G. Stem cell policy. Can adult stem cells suffice? Science 2001 Jun 8;292(5523):1820-2 I'm sorry to say that I have not read all these papers, I have read those that I have access to, such as the PNAS ones, but in some cases I have had to make do with the abstracts, in true undergraduate essay tradition. I certainly feel there is no strong moral grounds for not proceeding with either ES or human ES cloning research. I simply feel that there is too strong a bias towards embryonic stem cell research to the detriment of other possible avenues, this is probably exacerbated by the pressure from so many quarters to have all stem cell research banned. I may not feel that ES research is the last best hope for a number of diseases, as it is sometimes portrayed, but I would certainly defend the scientists right to research it, not neccessarily to the death I'm afraid, we all have our limits.

04-23-2003, 10:21 AM	#5
ps418 Veteran Member Join Date: Mar 2001 Location: Louisville, KY, USA Posts: 1,840	A new source of stem cells has been announced -- the pulp of 'baby teeth.' Other than nerve and dentin cells, Its not yet known what types of cells these stem cells can differentiate into. Contrary to what the press release below suggest, the paper does not seem to have been published yet. Scientists discover unique source of stem cells In other stem cell news, a paper published in the American Heart Association's journal, Circulation, reports a signficant improvement of heart function following 15 small intracardial injections of bone-marrow derived stem cells. The injections were accomplished using a new device called a NOGA catheter, which allows researchers to pinpoint the desired injection site within the heart. The baseline ejection fraction (the fraction of total blood ejected per heartbeat) in the treated group increased from 20% to 29%, which means that the patients are still suffering from severe heart failure. Normal EF is 50% or higher. But who knows how much room for improvement there may be? Its still very good news. Stem cells improve heart function of seriously ill heart failure patients Perrin et al, 2003. Transendocardial, Autologous Bone Marrow Cell Transplantation for Severe, Chronic Ischemic Heart Failure. Circulation Published online before print April 21, 2003. Patrick

04-28-2003, 07:12 AM	#9
Wounded King Veteran Member Join Date: Mar 2003 Location: Edinburgh Posts: 1,211	The fact that WNT regulates embryonic stem cell proliferation in haematopoetic populations is supremely unsurprising. Id imagine that a number of FGFs, BMPs and all the other usual supects of the developmental biology world will perform the same sort of tasks in ES populations as they do in the developing embryo. Austin TW, Solar GP, Ziegler FC, Liem L, Matthews W. A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells. Blood. 1997 May 15;89(10):3624-35. Van Den Berg DJ, Sharma AK, Bruno E, Hoffman R. Role of members of the Wnt gene family in human hematopoiesis. Blood. 1998 Nov 1;92(9):3189-202. Lako M, Lindsay S, Lincoln J, Cairns PM, Armstrong L, Hole N. Characterisation of Wnt gene expression during the differentiation of murine embryonic stem cells in vitro:role of Wnt3 in enhancing haematopoietic differentiation. Mech Dev. 2001 May;103(1-2):49-59.

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