ASTM...The NIH has only issued 17 clinical alerts since 1991..
The last one was in 1997; the one before that was 1995.
I attach the information from the NIH which explains how important these alerts are. As you can see, we are only beginning to hear the news about ASTM; this IS BIG!!
Also, as the attached citations from the medical literature show, ASTM is also VERY involved in technologies and techniques that may offer a cure for breast cancer, as well as many other things. Also, I have only included a few of the most recent citations; as you can see, however, ASTM does publish important papers rather frequently.
FWIW, I'm glad I held onto my shares; I hope to be able to buy some more cheap, but I think the cheap shares are already had!!
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NLM began offering clinical alert notices online in January
1991. Clinical alerts are provided to expedite the release of
findings from the NIH-funded clinical trials where such release
could significantly affect morbidity and mortality. Links to
clinical alerts are provided below. The availability of new
clinical alerts is announced in the MEDLARS broadcast
message.
There are currently 17 clinical alerts:
Periodic Transfusions Lower Stroke Risk in Children with
Sickle Cell Anemia
National Heart, Lung, and Blood Institute (NHLBI)
September 18, 1997
Adjuvant Therapy of Breast Cancer - Tamoxifen Update.
National Cancer Institute (NCI)
November 30, 1995
*****
This first article does not mention Aastrom, specifically, but it shows the importance and relevance. The rest are all written by Aastrom personnel.
Bone Marrow Transplant 1998 Jul;22 Suppl 1:S78-9
Cord blood transplantation (CBT) in
hemoglobinopathies. Eurocord.
Miniero R, Rocha V, Saracco P, Locatelli F, Brichard B,
Nagler A, Roberts I, Yaniv I, Beksac M, Bernaudin F,
Gluckman E
Eurocord Transplant Registry, Unite de Recherche, Hopital
Saint-Louis, Paris, France.
Patients with beta-thalassemia (Hbeta th) and sickle cell anemia
(SCA) can be treated with bone marrow transplantation. Stem
cells from cord blood have several theoretical advantages,
however, the place of cord blood transplant for
hemoglobinopathies has not yet been established. We report
here the EUROCORD experience of 10 patients (Hbeta th =
7, SCA = 3) transplanted with related cord blood.
Publication Types:
Clinical trial
*********
Bone Marrow Transplant 1998 Apr;21(7):653-63
Clinical-scale human umbilical cord
blood cell expansion in a novel
automated perfusion culture system.
Koller MR, Manchel I, Maher RJ, Goltry KL,
Armstrong RD, Smith AK
Aastrom Biosciences Inc., Ann Arbor, MI 48105, USA.
Use of umbilical cord blood (CB) for stem cell transplantation
has a number of advantages, but a major disadvantage is the
relatively low cell number available. Ex vivo cell expansion has
been proposed to overcome this limitation, and this study
therefore evaluated the use of perfusion culture systems for CB
cell expansion. CB was cryopreserved using standard methods
and the thawed unpurified cells were used to initiate small-scale
cultures supplemented with PIXY321,flt-3 ligand, and
erythropoietin in serum-containing medium. Twelve days of
culture resulted in the optimal output from most CB samples.
Frequent medium exchange led to significant increases in cell
(93%), CFU-GM (82%) and LTC-IC (350%) output as
compared with unfed cultures. As the inoculum density was
increased from 7.5 x 10(4) per cm2 to 6.0 x 10(5) per cm2,
the output of cells, CFU-GM, and LTC-IC increased. Cell and
CFU-GM output reached a plateau at 6.0 x 10(5) per cm2,
whereas LTC-IC output continued to increase up to 1.2 x
10(6) per cm2. Because the increase in culture output did not
increase linearly with increasing inoculum density, expansion
ratios were greatest at 1.5 x 10(5) per cm2 for cells (6.4-fold)
and CFU-GM (192-fold). Despite the lack of adherent stroma,
CB cultures expressed mRNA for many growth factors
(G-CSF, GM-CSF, IL-1, IL-6, LIF, KL, FL, Tpo,
TGF-beta, TNF-alpha, and MIP-1alpha) that were also found
in bone marrow (BM) cultures, with the exception of IL-11
(found only in BM) and IL-3 (found in neither). Culture output
was remarkably consistent from 10 CB samples (coefficient of
variation 0.3) indicating that the procedure is robust and
reproducible. Two commercial serum-free media were
evaluated and found to support only approximately 25% of the
culture output as compared with serum-containing medium.
Implementation of optimal conditions in the clinical scale,
automated cell production system (CPS) showed that the
process scaled-up well, generating 1.7 x 10(7) CFU-GM
(298-fold expansion) from 1.2 x 10(8) thawed viable nucleated
CB cells (n = 3). The ability to generate >10(7) CFU-GM
from <15 ml of CB within this closed, automated system
without the need for extensive cell manipulations will enable
clinical studies to test the safety and efficacy of expanded CB
cells in the transplant setting.
******
Bone Marrow Transplant 1998 Jul;22(2):153-9
Ex vivo expansion of bone marrow
from breast cancer patients:
reduction in tumor cell content
through passive purging.
Lundell BI, Vredenburgh JJ, Tyer C, DeSombre K, Smith
AK
Aastrom Biosciences, Ann Arbor, MI 48105, USA.
High-dose chemotherapy (HDC) with hematopoietic support
appears promising in the treatment of breast cancer, although
reinfusion of contaminating tumor cells may contribute to
disease relapse. Ex vivo expansion may reduce tumor cell
content through use of a small inoculum volume and by passive
purging during culture. We assessed the ex vivo expansion
potential of tumor cell positive bone marrow (BM) from breast
cancer patients and the effect of ex vivo expansion on tumor
cell content. Cryopreserved/thawed mononuclear cell (C/T
MNC) BM harvests with known tumor cell contamination (n =
7) were assessed for tumor cells pre- and post-expansion using
immunocytochemical (ICC) staining. Pre-expansion inoculum
samples contained a range of 6-2128 tumor cells per 5.0 x
10(6) nucleated cells. Ex vivo expansion resulted in fold
expansions of 6.67 and 11.37 for total cells and CFU-GM,
respectively. Tumor cells were undetectable in four of the seven
post-expansion samples and were reduced in the remaining
three samples. The data demonstrate passive purging of breast
cancer cells during ex vivo expansion, with hematopoietic
progenitor cell expansion comparable to that of normal BM.
Reduction in tumor cell number contained in the small volume
culture inoculum combined with passive purging during the ex
vivo expansion process suggest a potential 2-4+ log reduction
in tumor cell content in the reinfused cell product.
********
J Hematother 1998 Oct;7(5):413-23
Alternatives to animal sera for
human bone marrow cell expansion:
human serum and serum-free media.
Koller MR, Maher RJ, Manchel I, Oxender M, Smith
AK
Aastrom Biosciences, Inc., Ann Arbor, MI 48106, USA.
[Medline record in process]
The increasing use of cultured human cells in clinical trials is
highlighting the need for alternatives to media containing animal
sera that are typically used to support these cultures. Perfused
cultures of BM mononuclear cells (MNC) were used to
evaluate animal sera alternatives with respect to the output of
primitive, progenitor, and stromal cells. A serum level of 20%
was optimal, and this could be provided by FBS alone or by a
mixture of horse serum (HoS) and FBS, but not by HoS alone.
Allogeneic human plasma (20%) supported half the level of cell,
CFU-GM, and LTC-IC output as compared with animal
sera-containing control. Significant donor-to-donor variability in
human plasma was observed, but this was mitigated by pooling
of plasma samples. Autologous and allogeneic human plasma
performed equivalently. The use of autologous or allogeneic
human serum was found to be equivalent to the use of human
plasma, but all were inferior to animal sera. Animal sera
supported typical stroma and cobblestone formation, whereas
stroma in human serum cultures was less dense. Eight
commercial serum-free media were tested and found to support
MNC expansion to varying degrees, but none approached the
performance of the animal serum-containing control, particularly
with respect to stromal (i.e., CFU-F) support. In fact, when
MNC were cultured in parallel with CD34-enriched cells,
output (from MNC) was higher only in control medium,
apparently because serum-free media reduced accessory cell
effects. Because of these results, a new serum-free medium
was developed for MNC cultures. This formulation
outperformed all commercial serum-free media, resulting in cell
and LTC-IC output equivalent to that of control. However,
CFU-GM and CFU-F output were 66% and 9% of control,
respectively. Precoating the culture surface with collagen
increased CFU-F (and Thy-1+ cell) output to control levels,
although CFU-GM output was still lower than control. The
addition of either fibronectin or PDGF had no measurable
effect, nor did the use of 5-100-fold greater concentrations of
growth factor supplementation. The serum-free medium also
increased CD41+ and CD61+ cell output to 150%-220% of
control levels. The development of this new serum-free medium
has potential for use in the perfused BM MNC culture systems
currently in clinical trials to test the efficacy of expanded cells
after cytoablative chemotherapy.
*****
Biotechnology (N Y) 1995 May;13(5):449-53
Clinical systems for the production of
human cells and tissues.
Armstrong RD, Ogier WC, Maluta J
Aastrom Biosciences, Ann Arbor, MI 48106, USA.
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There are tons of other citations, but this is way too long as it is; but, it provides some important info for anyone who might be thinking about ASTM. Given that this offers a solution to the number one item on the NIH critical alert list, I suspect we will be hearing more.
Ed |
