A Stem Cell Core Facility for Studying Human Embryonic Stem Cell Differentiation

A Stem Cell Core Facility for Studying Human Embryonic Stem Cell Differentiation

Funding Type: 
Shared Labs
Grant Number: 
CL1-00508-1.2
Award Value: 
$1,679,818
Stem Cell Use: 
Embryonic Stem Cell
iPS Cell
Status: 
Active
Public Abstract: 
This application proposes to develop a Stem Cell Core Facility of ~1700 square feet to support the use of human embryonic stem cells (hESC) for a growing consortium of stem cell scientists at the home institution as well as neighboring institutions. The facility will be built and managed so as to allow use of non-NIH-approved hESC cell lines as well as research funded by non-federal agencies including the California Institute for Regenerative Medicine (CIRM). The Facility will be centrally located adjacent to other existing, successful core facilities and within short walking distance of all the users at the home institution. The Facility will be managed by an Oversight Committee consisting of faculty experienced in hESC and associated technologies, as well as those with experience in managing shared core facilities. The Committee will have close contact with an established Biotechnology Impacts Center to address any ethical issues that may arise. The users at the home institution consist of an energetic, interdisciplinary group of both young and established investigators who have made a substantial commitment to stem cell biology. Within the past several years, they have held workshops on embryonic stem cells with neighboring institutions, taught two graduate level courses in stem cell biology, including one in bioethics, established a Stem Cell Center, and applied for and received CIRM funding. They have recently hired an experienced hESC investigator and are currently recruiting others, demonstrating the home institution’s commitment to the field of hESC. The group currently consists of 30 investigators from three different colleges within the home institution who have common interests in molecular mechanisms of pluripotency and differentiation of hESC. Several investigators have joint projects, including collaborations with investigators at neighboring institutions who will also be using the facility. The proposed Stem Cell Core Facility will allow this dynamic group of accomplished investigators to bring the promise of stem cell biology to an expanding, culturally diverse region of California. The research programs that would use the facility concentrate on various aspects of the molecular mechanisms underpinning the pluripotency of hESC, as well as their ability to differentiate into different types of tissues. The results generated by these programs will contribute to the development of tools, diagnostics, and therapies by laying the foundation for understanding hESC and identifying new compounds and methodologies that will allow researchers to maintain hESC and prepare them for use in therapies. This basic understanding of the molecular networks governing hESC biology is essential before any safe and effective treatment can be considered for use in humans.
Statement of Benefit to California: 
When Californians resoundingly passed Prop 71, they demonstrated the importance of stem cell research to all the citizens of our state. However, the human embryonic stem cell (hESC) lines that are currently sanctioned by the federal government are limited by many factors including genetic stability, contamination, poor growth characteristics, and lack of genetic and disease diversity. Working with non-federally approved hESC lines, including new more robust lines that will be developed in the future, will be necessary for any eventual therapeutic use of stem cells. Also critical to that success will be a thorough understanding of the molecular mechanisms that govern the pluripotency and differentiation of hESC, as well as attracting new scientific expertise to the field of stem cell biology. This proposal meets these challenges and benefits all Californians by establishing a Stem Cell Core Facility (SCCF) that will greatly expand both the scientific as well as the geographic base of stem cell research. The SCCF will allow research on non-federally funded hESC lines and service a group of highly accomplished investigators at the host and neighboring institutions in the most ethnically and culturally diverse and fastest growing region of California. The investigators are all at the top of their respective fields, have a range of hESC expertise and are committed to applying their experience to some of the most critical issues facing the hESC field today. The group is highly interdisciplinary and has an established history of productive interactions and collaborations. They have created a new Stem Cell Center which is aggressively fostering stem cell research and have secured extramural funding for that research. All proposed users have existing projects that directly impact our understanding of the basic biology of hESC and will generate data that will be essential to the successful development of stem cell-based therapies.
Progress Report: 

Year 1

This year has been devoted to hiring staff to operate the Core, purchasing and setting up Core equipment, officially opening the Core for stem cell research, and teaching two stem cell culturing courses in the Core. On August 1, 2010, we hired an Academic Coordinator to oversee operation of the Core. He played a vital role in purchasing equipment and preparing for the opening of the Core. In addition, the Academic Coordinator has been responsible for day-to-day operations of the Core since it opened for general use, for training users, and for overseeing the Core staff. Between August 1, 2009 and the official opening on January 29, 2010, we evaluated and purchased most of the equipment for the lab, had equipment installed, and underwent training on the new equipment. The Core offers three cell culture suites, an equipment room, an analytical room, a microscopy room, and a cytogenetics workstation. In September 2009, the Core hosted the CIRM site visit team which toured the facility prior to its completion. In December, we hired a temporary staff member who also helped prepare the lab for opening in January. The UCR Stem Cell Core Facility opened officially on January 29th 2010, and a day long Grand Opening event was held. This was attended by over 200 people from UCR, other California campuses, high school teachers, and members of the community. The Grand Opening featured tours of the Core, information on accessing and using the Core, lectures, a poster session, and an image contest. We also launched a website for the Core which contains complete information on the facility, as well as the resources and services offered by the Core. The website can be found at www.stemcellcore.ucr.edu . The Core also set up a Sales and Services operation to enable users to buy most items needed for their research from the Core. This has been very successful and has facilitated use of the Core. Since the official opening, we have had extensive use of the Core equipment and culture facilities. We have provided lab space for culturing stem cells for faculty who can not culture in their home labs. Users can also purchase stem cell cultures from the Core for their research. We also offer state-of-the art equipment which has been extensively used by our stem cell labs at UCR. Some of our equipment is available only at the UCR Core (e.g., we have a Nikon BioStation CT that enables high content collection of time lapse video data of dynamic cellular processes). In April, we taught a one week hands-on laboratory course to Bridges students from California Polytechnical Institute (Pomona), and in June, we taught a two week human embryonic stem cell culturing course for credit (CMDB 211) to UCR graduate students. The Core hired two new temporary staff this July. These staff help with inventories, ordering, maintaining and passaging cultures, and free-up time for the Academic Coordinator to work with faculty and students on their projects. Data collected in the Core were presented in posters at the annual meetings of the International Society for Stem Cell Biology in June 2010, and a paper using Core equipment was published in May 2010. Our faculty have been using the Core to conduct research dealing with differentiation of bone cells, wound healing, differentiation of endoderm, scaling up procedures for growth of pluripotent stem cells, creating new lines of reporter cells, creating induced pluripotent stem cells, and evaluation of environmental toxicants using stem cells. To bring stem cell information to the local community, the Core has been engaged in numerous outreach activities. We have hosted many tours through the Core and provided information and help to others in the Riverside/San Bernardino area who are working with stem cells. We are currently preparing to offer workshops on the use of Core equipment to introduce new users to the capabilities of the Core and to facilitate use of the Core.

Year 2

This year was spent hiring staff to assist in operation of the Core, purchasing Core equipment, helping researchers begin stem cell projects, hosting CIRM Bridges students, teaching stem cell culturing courses, and taking full advantage of the research facilities offered by the Core. Our Academic Coordinator oversees daily operation of the Core, trains new users, and oversees the Core staff. Two temporary staff supported the Core from June 2010 through the early part of 2011. These staff helped with inventories, ordering, maintaining and passaging cultures, and thereby freed-up time for the Academic Coordinator to work with faculty and students on their projects. A new staff member, highly experienced in cell culture, was hired in April 2011 and currently provides support to the Academic Coordinator and users of the Core. The Core offers three cell culture suites, an equipment room, an analytical room, a microscopy room, and a cytogenetics workstation. The Core also offers state-of-the art equipment which has been extensively used by our stem cell labs at UCR. Some of our equipment is available only at the UCR Core (e.g., the Nikon BioStation CT that enables high content collection of time lapse video data of dynamic cellular processes). The Core was very fortunate this year to receive about 1700 square feet of new space adjacent to the existing Core. This new space, the Stem Cell Core Annex I, will provide us with a conference room, storage space, a new culture room, microscope room, and additional office space for Core users. The addition of this new space will greatly enhance Core operations, enable growth, and allow us to expand Core activities in the future. The Core offered a stem cell culturing class during spring quarter which was taken by CIRM Bridges students and UCR graduate students. We accepted our first group of CIRM Bridges students from California State University at San Bernardino this spring. The Bridges students are currently doing internships in UCR host labs. The Core also supported a new course in live cell imaging and analysis (EE272) which used human embryonic stem cells in most of its lab projects. The Core continues to offer a Sales and Services operation to enable users to buy most items needed for their research from the Core at a reduced cost to the user. This has been very successful and has facilitated use of the Core. The Core facilities have received extensive use and have provided lab space for faculty who cannot culture cells in their home labs. Users have also purchased stem cell cultures from the Core for their research projects. Data collected in the Core were presented in posters at the numerous meetings this year, and our stem cell laboratories published 17 new papers that included data collected in the Core. Our faculty have been using the Core to conduct research dealing with osteogenesis, wound healing, primordial germ cell differentiation, testing scaffolds for tissue repair, differentiation of endoderm, differentiation of microglia, scaling up procedures for growth of pluripotent stem cells, and evaluation of environmental toxicants using stem cells. The Core has created 35 new lines of induced pluripotent stem cells (iPSC) from human fibroblast and 8 iPSC lines from COPD patients. The latter lines open the opportunity for Core users to study COPD in a dish. The Core has also created reporter lines of hESC and human iPSC which are available to stem cell researchers. To bring stem cell information to the local community, the Core has been engaged in numerous outreach activities. We have hosted tours through the Core, given lectures at local universities, and provided information and help to others in the Riverside/San Bernardino/Palm Springs area who are working with stem cells. The Core maintains a website which contains complete information on the facility, as well as the resources and services offered by the Core (www.stemcellcore.ucr.edu).

Year 3

This year the Core provided facilities and training to an increasing number of stem cell research labs. We have added four new stem cell labs to our Stem Cell Center at UCR, and each lab has undergone training in the Core and had their lab members perform work in the Core. The new labs all have an interest in developing scaffolding for growing stem cells in 3-dimensions and have made innovative progress in this area. We have also offered hands-on training courses to 12 CIRM Bridges students from two universities and to five UCR graduate students. Five new CIRM Bridges students began their internships on our campus this year, and two CIRM interns from last year have continued on to complete a full year of training at UCR. The latter two students have received Master’s degrees and are now entering PhD programs. We have continued to develop new reporter lines in the Core and to make these available to other users and we have further characterized our RIV9 induced pluripotent stem cell line. This year we added a significant amount of space to the Core, almost doubling it in size. This space now accommodates several pieces of equipment, including the flow cytometer, microplate reader, Luminex, and karyotyping workstation. The new space also provides office space for students and an upgraded conference room. Users of the Core have presented their work at numerous conferences and published their data in a wide range of journals. UCR was instrumental in forming the Inland Empire Stem Cell Consortium to bring together stem cell researchers in our geographic area. We continue to maintain an up-to-date a website for the Core which contains complete information on the facility, as well as the resources and services offered by the Core. The website can be found at www.stemcellcore.ucr.edu. The Core also operates Sales and Service to enable users to buy most items needed for their research directly from the Core. This has been very successful and has facilitated stem cell work on our campus. Our faculty have been using the Core to conduct research dealing with differentiation of bone cells, wound healing, differentiation of endoderm, scaling up procedures for growth of pluripotent stem cells, creating new lines of reporter cells, creating induced pluripotent stem cells, development of 3-dimentsional scaffolds, angiogenesis, and evaluation of environmental toxicants using stem cells. To bring stem cell information to the local community, the Core has been engaged in outreach activities. We have hosted many tours through the Core and provided information and help to others in the Riverside/San Bernardino area who are working with stem cells.

Year 4

This year the UCR Stem Cell Core hired new staff to assist in operation of the Core, revamped the organization of the Core to improve it operation, provided space and cells for stem cell research, helped researchers develop their stem cell projects, hosted CIRM Bridges students, hired new staff, and took full advantage of the research facilities offered by the CIRM-funded Core. Our new Academic Coordinator oversees daily operation of the Core, trains new users, and oversees the Core staff. She has been involved in implementing changes to facilitate operation, interface with the Office of Research, develop new training opportunities in the Core, and upgrade Core equipment. A permanent staff position was filled in the fall, and this person helps with daily operation of the Core, provides cells to Core users, maintains inventories and places orders. A temporary position was filled to help with reorganization of Core Sales and Services, upgrade the website, and help with equipment maintenance and repair. The Core offers three cell culture suites, an equipment room, an analytical room, a microscopy room, and a cytogenetics workstation. The Core also offers state-of-the art equipment which has been extensively used by our stem cell labs at UCR. Some of our equipment (e.g., the Nikon BioStation CT) has also been used by stem cell labs at Loma Linda University and our Core provides storage for cells generated by a local Biotech company. Last year, the Core was fortunate to receive about 1700 square feet of new space adjacent to the existing Core. This new space, the Stem Cell Core Annex I, provides us with a conference room (which was upgraded this year), storage space, a microscope room, and additional office space for Core users. The addition of this new space has greatly enhanced Core operations, enabled growth, and allowed us to expand Core activities. This year we moved much of our expendable supply inventory into the Annex space and thereby freed-up valuable floor space in the main Core making operations in the culture area easier to perform and creating a better sterile environment. The Core is preparing to offer a stem cell culturing class this September to UCR students. We accepted six new CIRM Bridges students from California State University at San Bernardino this spring, and they do part of their work in the Core. The Core also supported a course in live cell imaging and analysis (EE272) which used human embryonic stem cells in all of its lab projects. The Core continues to offer a Sales and Services operation to enable users to buy most items needed for their research from the Core at a reduced cost to the user. The inventory system for Sales and Services was upgraded this year, and the method for distribution and storage of our inventory was improved. This has greatly facilitated use of the Core. The Core facilities have received extensive use and have provided lab space for faculty who cannot culture cells in their home labs. Four labs from the College of Engineering work in the Core daily and have assigned spaces. Users can also request the Core grow cells for their research projects to help move projects along efficiently. Data collected in the Core were presented in platform and poster sessions at the numerous meetings this year, and five of these presentations won first place awards. The laboratories using the Core published 22 papers this year that incorporated stem cell work done in the Core. Three of our stem cell graduate students who use the Core won NSF pre-doctoral fellowships and one graduate student received an NIH pre-doctoral fellowship to support her work with stem cells. Our faculty have been using the Core to conduct research dealing with osteogenesis, wound healing, primordial germ cell differentiation, testing scaffolds for tissue repair, differentiation of endoderm, scaling up procedures for growth of pluripotent stem cells, and evaluation of environmental toxicants using stem cells. The Core has created 35 new lines of induced pluripotent stem cells (iPSC) from human fibroblasts. The Core has also created reporter lines of hESC and human iPSC which are available to stem cell researchers. To bring stem cell information to the local community, the Core has been engaged in outreach activities. We have hosted tours through the Core, given lectures at local universities, and provided information and help to others in the Riverside/San Bernardino/Palm Springs area who are working with stem cells. The Core maintains a website which contains complete information on the facility, as well as the resources and services offered by the Core (www.stemcellcore.ucr.edu).

Year 5

During 2013-14, the UCR Stem Cell Core revamped the organization of the Core to improve it operation, registered all Core users, provided space and cells for stem cell research, helped researchers develop their stem cell projects, upgraded and serviced equipment, hosted CIRM Bridges students, offered a hands-on human embryonic stem cell training class twice, trained new staff, evaluated cells lines derived in the Core, beta tested new culture medium, laid the ground work for isolating new lines of human embryonic stem cells, presented at scientific meetings, engaged in outreach activities, and took full advantage of the research facilities offered by the CIRM-funded Core. Our Academic Coordinator oversaw daily operation of the Core, created standard operating protocols for all major Core equipment, trained new users, offered monthly training on equipment, organized a vendor show, and oversaw the Core staff. She interfaced with the Office of Research to complete the paperwork necessary for deriving new human embryonic stem cell lines. A permanent staff technician helped with daily operation of the Core, provided cells to Core users, maintained inventories, handled operations and billing for Sales & Services, trained users on equipment in the Core, and placed orders for the Core. A part-time administrative assistant helped with reorganization of Core Sales and Services, upgrading the website, upgrading computers and troubleshooting computers problems, and helped with equipment maintenance and repair. The Core offers three cell culture suites, an equipment room, an analytical room, a microscopy room, and a cytogenetics workstation. The Core also offers state-of-the art equipment which has been extensively used by our stem cell labs at UCR. Some of our equipment (e.g., the Nikon BioStation CT) has also been used by stem cell labs at Loma Linda University, and our Core provides storage for cells generated by a local Biotech company. This year, the Stem Cell Core Annex, which is new space acquired several years ago, was upgraded with new flooring. Workstations in the Annex were also upgraded with new image processing software. The Core has organized a two-day hands-on training session for video analysis software that will take place this August. The Core also taught a hands-on stem cell culturing class in September to UCR students and again offered this class to both CIRM Bridges students and UCR in the spring quarter (2014). We accepted three new CIRM Bridges students from California State University at San Bernardino this spring, and they do part of their work in the Core. The Core continues to offer a Sales and Services operation to enable users to buy most items needed for their research from the Core at a reduced cost to the user. The inventory system for Sales and Services was upgraded, and the method for distribution and storage of our inventory was improved. This has greatly facilitated use of the Core. The Core facilities have received extensive use and have provided lab space for faculty who cannot culture cells in their home labs. Four labs from the College of Engineering work in the Core daily and have assigned spaces. Users can also request the Core grow cells for their research projects to help move projects along efficiently. Data collected in the Core were presented in platform and poster sessions at the numerous meetings this year, and a number of these presentations won awards. The laboratories using the Core published 22 papers in a broad spectrum of engineering and life science journals. Two of our stem cell graduate students who use the Core won pre-doctoral fellowships from the NSF and Tobacco-Related Disease Program of California. Our faculty have been using the Core to conduct research dealing with osteogenesis, wound healing, testing scaffolds for tissue repair, differentiation of endoderm, scaling up procedures for growth of pluripotent stem cells, modulating differentiation will tunable scaffolds, identifying stem cell factors that promote motility, and evaluation of environmental toxicants using stem cells. This year the Core evaluated the pluripotency and differentiation capability of the induced pluripotent stem cells that we derived previously. The Core website has been fully upgraded and contains complete information on the facility, as well as the resources and services offered by the Core (www.stemcellcore.ucr.edu). The Core introduced karyotyping into its repertoire of services and now performs karyotyping and g-banding in house. To bring stem cell information to the local community, the Core has been engaged in outreach activities. We have hosted tours through the Core, given lectures at local universities, provided information and help to others in the Riverside/San Bernardino/Palm Springs area who are working with stem cells and participated in events sponsored by patient advocate groups.

© 2013 California Institute for Regenerative Medicine