Molecular Vision policy on use of cell lines: Compulsory authentication
Manuscripts reporting experiments in which immortalized cell
lines are used must include data and documentation
that demonstrate that the actual cells used in the experiments
reported in the manuscript exhibit the correct phenotype and
genotype. Authors are must read the article written by the editors on the authentication of cell lines (). In brief, authors must demonstrate that the cells actually used
are of the correct species of origin, the correct sex and
genotype, and express genes and gene products that are specific
to the pertinent cell type.
It is expected that the cell line expresses genes necessary for hypothesis testing. This may require specific differentiation. Regardless, correct expression must be documented in the manuscript.
Submissions that use primary cell cultures or animals to verify
hypotheses tested first in immortalized cell lines will be viewed in general more favorably than work that relies solely on cell lines.
The critical policy, criteria, and instructions for meeting these criteria are quoted here from that article:
"Molecular Vision policy on use of cell lines: Compulsory authentication
The editors of Molecular Vision recognize that the proper use of immortalized cell lines can result in the rapid generation of substantial data in testing many hypotheses. However, due to continual problems of misidentification of cell lines for at least 55 years [24-28], including estimates of mammalian cell misidentification of 15%-35% [27,29,30], the new Molecular Vision policy for reporting data based on immortalized cell lines is:
Manuscripts reporting experiments in which immortalized cell lines are used must include data, documentation, and citations that demonstrate that the actual cells used in the experiments reported in the manuscript exhibit the correct phenotype and genotype. It must be demonstrated that the cells actually used are of the correct species of origin, the correct sex and genotype, and express genes and gene products that are specific to the pertinent cell type. Where possible, phenotype analysis should include the effects of differentiation. Cells used in experiments should be within a few passages of authentication (typically five passages). These standards hold even if the cell lines are considered "established" and were obtained from reputable sources. A statement of cell handling protocol that includes passage information and authentication data, certification documentation, and/or citation of published authentication by the co-authors must be provided in Methods sections of submitted manuscripts. These will be part of the freely-available article.
Meeting these criteria
Authors are encouraged to study the history and consequences of misidentification of cell lines and the array of solutions available to avoid this chronic problem. Several excellent reviews and primary papers are available (e.g., [22,24-28,31]). Even a cursory reading of these sources provides insight into the historical lack of scientific rigor and expensive outcomes in terms of research monies and careers that has plagued the misuse of immortalized cell lines.
The editors of Molecular Vision agree with The International Cell Line Authentication Committee (ICLAC) and the National Institutes of Health (NIH) in their statements of the need for cell line authentication (NOT-OD-08-017) and approaches to accomplish this authentication [25]. The ICLAC provides guidelines for incorporating authentication into good tissue-culture practice (Advice to Scientists: Incorporating Authentication into Everyday Culture Practice). A similar online resource is published by the National Center for Biotechnology Information [30]. Briefly, once a cell line is authenticated, it is expanded to create a "master stock" of cell aliquots for cryopreservation. An aliquot from the master stock is expanded to create a "distribution stock" of cell aliquots. An aliquot from the distribution stock is expanded into aliquots of cells that are used in the actual experiments reported in submitted manuscripts. Thus, by best practices, the cells actually used in experiments should be within five passages of authentication (this is not five passages from the initial establishment of the cell line, which may have occurred many passages earlier). These guidelines must be followed and documented in order for data based on the use of immortalized cell lines to be published in Molecular Vision. Exemptions for incidental use of immortalized cells (e.g., simple expression confirmation assays) might occur following scrutiny by reviewers and editors. The journal’s Instructions to Authors will contain the above policy statement and supporting details, including examples of potential exceptions.
Authentication itself principally involves short-tandem-repeat (STR) profiling using standards and protocols developed by the American National Standards Institute for human cell lines [30,32] and by the National Institute of Standards and Technology for mouse cell lines [33]. The articles reporting the re-characterization of the RGC-5 cell line also provide insight into authentication approaches [20,22,23]. Cell lines also may be authenticated by replicating the experiments published for initial characterization. Authors can either provide data in their submitted manuscripts demonstrating that cell lines were authenticated by these various standards, or they can contract with external services (e.g., ATCC, Promega, Identicell, DSMZ, Genetica, and others not listed) to provide authentication. If contract services are used, documentation from the service must be supplied to Molecular Vision as part of the manuscript submission. Note that only some, but not all, cell lines sold by commercial suppliers are authenticated. It is the authors' responsibility to confirm authentication."
authors will be held to those standards in the editorial ().
the RGC-5 cell line to model retinal ganglion
cell line was originally reported to be derived from postnatal
day 1 rat retina cells, expressed markers specific &to
retinal cells, and was sensitive to trophic factor withdrawal
and glutamate toxicity following treatment with
differentiation factors (Krishnamoorthy
et al., Brain Res Mol Brain Res. -2):1-12).
Several research groups report that even cells obtained from
the originating laboratories are not of rat origin and do not
express genes and proteins specific to retina or retinal
ganglion cells (e.g., Van
Bergen et al., IOVS 7-4272, Krishnamoorthy
et al., Invest Ophthal Vis Sci. 2-5719)
New manuscripts containing data derived
from RGC-5 cells will be editorially rejected without review.
Negative Data
Studies of a negative nature are accepted only
if the logic for carrying out the experiment is compelling, it
is highly likely that other groups in the field would
inevitably perform the same futile studies repeatedly, and
such a report would warn them away from wasting time and
money. Studies showing an inability to confirm previously
reported association or linkage data will be considered
depending on comparability to the original study in terms of
disease phenotype, population of interest, methodology, and
the power of the repeat study to exclude association or
linkage (e.g., 95% probability limits for the odds ratio).
Submission of manuscripts:
New manuscript submissions should use our online submission system.
Instructions for warranting author
responsibilities and contributions are handled within the
online submission system. Each and every author must
personally answer these queries. Please assure that all author
names and email addresses are correct and current when
submitting your manuscript. Each author must have his/her own
unique email address. The corresponding author is not
authorized to answer on behalf of the other authors. US
government employees must answer the same set of questions
online as other authors. Errors at this step will greatly
delay the completion of the submission process and block the
review process.
Author Responsibilities, Licensing, and
Copyrights:
Each author shall sign an online statement
warranting that he/she authored the work, actively
participated in the reported experiments, and he/she approves
and agrees with representation of the data in the article.
Each author shall warrant that the article is original, is not
being considered for publication by another journal, and has
not been previously published other than as an abstract.
Each author shall sign an online statement that,
if the article is accepted for publication, the article and
all supplementary materials will be made freely available
online immediately with a Creative Commons
Attribution-NonCommercial-NoDerivatives License 3.0, or CC
BY-NC-ND 3.0 (see
http://creativecommons.org/licenses/by-nc-nd/3.0/ for license
terms). The authors retain copyright and grant Molecular
Vision an irrevocable, royalty-free, perpetual license to
publish and distribute the article, in all formats now known
or later developed, and to identify Molecular Vision as the
original publisher.
Competing interests
The authors shall declare any competing,
commercial, or conflicts of interests, regarding this
publication. Each author warrants this in the online
submission system.
Resubmission of revised Manuscripts
Revisions to active manuscripts shall be
resubmitted through the online manuscript system.
Do not submit a revised manuscript as a new
manuscript.
Notices about republication
For noncommercial use, republished material must
include a citation to the original work in Molecular Vision
and must not be changed from the original. See
http://creativecommons.org/licenses/by-nc-nd/3.0/ for license
Articles authored by a student may be reproduced
for inclusion in the student's thesis or dissertation, whether
in an online repository at the student's institution or
through a commercial service used by the student's
institution. Such republications must include a citation to
the original work in Molecular Vision and must not be changed
from the original. They do not require further permissions
from Molecular Vision for republication in a thesis or
dissertation submitted in partial fulfillment of requirements
for an advanced scholarly degree. CC BY-NC-ND 3.0 (see
http://creativecommons.org/licenses/by-nc-nd/3.0/ for license
terms) applies to derivative works other than the thesis or
dissertation.
Commercial publishers shall ask permission from
Molecular Vision to republish parts of an article. Specific
directions are online at Commercial
Permissions. The publisher also shall ask permission of
The Authors directly.
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