Cecilia Götherström group

Cells derived from perinatal tissues have great clinical potential. The pregnancy is a source of stem cells, with potential applications in medicine. However, the best source, isolation and culture method is to be established for each area of use.

Cells derived from the fetus and membranes have more potential than cells derived from adult tissues. Promising candidates are multipotent mesenchymal stromal cells (MSC).

The interest in these cells is based on their multipotentiality, immunomodulatory, anti-inflammatory and tissue repairing effects in combination with a minimal oncogeneic risk.

Keywords: Fetal stem cells, mesenchymal stem cells, prenatal transplantation, cord blood

Members

Cecilia Götherström, Group Leader.
Phone: +46 (0)8-524 880 64 

She defended her PhD at Karolinska Institutet in 2004. After a Post Doc at Imperial College London, she received a scholarship to continue her research at Karolinska Institutet. Now she is an Associate Professor in Stem Cell Research and holds an Senior Researcher position at CLINTEC, Division of Obstetrics and Gynecology. She has a research group at HERM and manage the National Cord Blood bank at Karolinska University Hospital.

Åsa Ekblad, PhD student, Master of Science in Engineering. 
Phone: +46 (0)73-941 5132

My PhD project is about autologous tissue engineering for the correction of congenital soft tissue defects. The aim is to find the best perinatal cellular source in combination with a carrier matrix to produce an autologous piece of extra tissue to use in the surgical correction of the defect shortly after birth. Åsa is also working half time with the production of fetal mesenchymal stem cells for the BOOSTB4 project. 

Ulrica Askelöf, Registered nurse, PhD student, Midwife. 
Phone: +46 (0)70-167 1366

Is currently doing her PhD project on “Challenges in collection of umbilical cord blood for clinical banking”. The first study is a clinical trial comparing iron status and hemoglobin in four months old children after different cord clamping methods. In study 2 she investigates the significance of mode of delivery and fetal stress for the composition of umbilical cord blood. Study 3 is an evaluation of intermediate umbilical cord clamping as an option in collection of umbilical cord blood for clinical banking and the last study examines parents’ experience of altruistic donation of UCB. 

 

Lilian Walther Jallow, BSc Chem, PhD, Senior Scientist, Research Coordinator for the BOOSTB4 project.
Phone: +46 (0)70 4151607

Lilian received her PhD from the Swedish Institute of Infectious Disease Control/Karolinska Institutet in 2000. She is a senior Scientist/Project leader with experience from academy, small size pharmaceutical industry as well as from postgraduate education within the pharmaceutical area. Now she is a research coordinator for the BOOSTB4 project with the aim to treat children with Osteogenesis Imperfecta pre- and postnatally with mesenchymal stem cells.
 

 

Annika Goos, BSc in Microbiology/Organic chemistry. 
Phone: +46 (0)76-650 6845

Annika received her BSc in 1982 and has worked in the small size pharmaceutical industry for more than 25 years. She has an extensive experience in early drug development and in vitro pharmacology. Annika is responsible for the production and quality control of fetal mesenchymal stem cells in the BOOSTB4 project. 

 

Nicolina Renkvist, University Certificate in Chemical Engineering, MSc in Molecular Biology, PhD, Senior Scientist, QA Responsible in the BOOSTB4 project. 
Phone: +46 (0)76-19 60 222

Nicolina received her PhD from the Open University in London in cooperation with the National Tumor Institute in Milan in 2003. After a Post Doc at the Ludwig Institute for Cancer Research in Brussels, she has worked as Senior Scientist and for the last 5 years she has focused on Quality Assurance (QA) within the Pharmaceutical Industry where she got experience from aseptic production of biological pharmaceuticals for clinical trials. Nicolina is currently responsible for QA questions in the BOOSTB4 project. 

 

Fawaz Abomarey, Bachelor and Honours degrees in Pharmacology, PhD student. 
Phone: +46 (0)73-909 6499

Fawaz completed his Bachelor and Honours degrees in Pharmacology from the University of Auckland, New Zealand. He is currently doing a PhD project titled 'Mesenchymal stem cells and Endometriosis'.

 

Maria Stefopoulou, MD, PhD student, Specialist in Obstetrics and Gynecology/Center for Fetal Medicine at Karolinska University Hospital. 
Phone: +46 (0)76-086 5880

Maria is currently doing a PhD project titled 'Prenatal Transplantation of Mesenchymal Stem Cells for Treatment of severe Osteogenesis Imperfecta'. The first part of her project is the clinical investigation of prenatally diagnosed severe skeletal dysplasias. In the second part she will examine if the size of the infusion needle affect the survival of MSC. In the third part she will evaluate the information and consent procedure in prenatal transplantation and in the last part she will examine the safety of prenatal transplantation. 

Research projects

Our overall aim is to evaluate the clinical potential and the significance of stem cells and progenitors obtained from fetal, amniotic, cord blood and placental tissues.

1. Developing new clinical treatment options using perinatal MSC

BOOSTB4

The BOOSTB4 clinical trial is an international multicenter study with funds from the European Commission Horizon 2020 and the Swedish Research Council and with Cecilia Götherström as Principal Investigator. The principal objective is to conduct a Phase I/II study of the safety and efficacy of pre- and/or postnatal MSC transplantation in the severest viable forms of Osteogenesis Imperfecta (OI). Transplantation before birth at the onset of disease should lead to greater efficacy and engraftment with less rejection than transplantation after birth. The BOOSTB4 consortium is led by experts in MSC, prenatal therapy and OI at the Karolinska Institutet (KI), and five additional EU Centers of excellence in The Netherlands, Great Britain and Germany are included in the clinical trial. 

Web site: BOOSTB4.EU

We are also developing treatments for:

  • Severe structural defects diagnosed before birth
  • Life threatening bronchopulmonary dysplasia and necrotizing enterocolitis in premature babies

 

2. Characterizing and comparing MSC from different perinatal sources

We work with many perinatal sources: fetal tissues (first trimester), amniotic fluid, chorionic villus, biopsies of muscle and skin (second trimester), umbilical cord blood, placenta, Wharton´s Jelly (term). These cells are evaluated for their potential in perinatal regenerative medicine. We also evaluate how maternal and fetal microchimerism, pregnancy, and mode of delivery affect the isolated cells.

 

3. Wait a minute - cord blood collection and clamping

Umbilical cord blood contains large amounts of unique blood stem cells that can be used to cure people with leukemia. However, lately late umbilical cord clamping has been proposed and applied in many hospitals in Sweden since late clamping has been associated with increased iron depots in the child. It is unclear how this relates to health and wellbeing of the infant. We are examining how clamping at 1 minute affects children's health status related to early (<10 seconds) or late (>3 minutes) clamping. We are also evaluating if it is possible to collect cord blood for clinical banking with clamping at 1 minute.

 

4. The role of mesenchymal stem cells in endometriosis

In endometriosis the endometrium of the uterus grows ectopically in the pelvic cavity, leading to inflammation, excruciating chronic pelvic pain and infertility. Current medical and surgical modalities are associated with high recurrence rate of symptoms and ectopic lesions, moreover, its pathogenesis still remains unclear. Mesenchymal stem cells are capable of modulating the immune response by sensing and simultaneously responding to their immediate microenvironment. Our aim is to examine if mesenchymal stem cells form part of the pathology of endometriosis.

Financial support

  • European Commission Horizon 2020 grant for the clinical trial BOOSTB4
  • The Swedish Research Council Clinical Therapy Research grant for the clinical trial BOOSTB4
  • Vinnova
  • The Children´s Cancer Foundation
  • Strategic ALF-grants for hematologic stem cell research
  • Swedish Medical Society
  • Magnus Bergvalls Society
  • Åke Olssons stiftelse för forskning inom haematologi
  • ALF
  • Jerringfonden

Selected publications

Amniotic fluid - a source for clinical therapeutics in the newborn?
Ekblad Å, Qian H, Westgren M, Le Blanc K, Fossum M, Götherström C.
Stem Cells Dev. 2015 Jun 15;24(12):1405-14.

Pre and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience
Götherström C, Westgren M, Shaw S, Åström E, Biswas A, Byers P H, Mattar C, Graham G H, Taslimi J, Ewald U, Fisk N M, Yeoh A, Lin J-L, Cheng P-J, Choolani M, Le Blanc K and Chan J.
Stem Cell Translational Medicine (2013) 2014 Feb;3(2):255-64. 

Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC.
Guillot P, Gotherstrom C, Chan J, Kurata H, Fisk N
Stem Cells 2007 Mar;25(3):646-54.

Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta.
Le Blanc K, Götherström C, Ringdén O, Hassan M, McMahon R, Horwitz E, et al
Transplantation 2005 Jun;79(11):1607-14

Immunologic properties of human fetal mesenchymal stem cells.
Götherström C, Ringdén O, Tammik C, Zetterberg E, Westgren M, Le Blanc K
Am. J. Obstet. Gynecol. 2004 Jan;190(1):239-45.

Links

HematologyRegenerative Medicine