Cecilia Götherström

Karolinska Institutet | KI · Department of Clinical Science, Intervention and Technology - CLINTEC

This two-paper Series focuses on recent advances and applications of regenerative medicine that could benefit paediatric patients. Innovations in genomic, stem-cell, and tissue-based technologies have created progress in disease modelling and new therapies for congenital and incurable paediatric diseases. Prenatal approaches present unique opportun...

Objectives There is a need for updated haematological reference data in infancy. This study aimed to define intervals for haemoglobin and red blood cell biomarkers based on data from a large cohort of longitudinally followed Swedish infants. Design Longitudinal cohort study. Setting Two Swedish study centres. Participants Three community-based p...

The aim of this study was to provide a brief overview on the background and rationale on treating fetuses and children suffering from osteogenesis imperfecta (OI) with mesenchymal stem cells (MSCs). MSCs ability to migrate, engraft, and differentiate into bone cells and to act via paracrine effects on the recipient's tissues makes these cells promi...

Scaffolds of recombinant spider silk protein (spidroin) and hyaluronic acid (HA) hydrogel hold promise in combination with cell therapy for spinal cord injury. However, little is known concerning the human immune response to these biomaterials and grafted human neural stem/progenitor cells (hNPCs). Here, we analyzed short- and long-term in vitro ac...

Background Osteogenesis Imperfecta (OI) is a rare genetic condition characterised by increased bone fragility. Recurrent fractures, pain and fatigue have a considerable impact on many aspects of the life of a person affected with OI and their families. Objective To improve our understanding of the impact of OI on the daily lives of individuals and...

The safety of mesenchymal stem cell therapy for osteogenesis imperfecta has been demonstrated previously. However, it is unknown how the trophic effects are mediated by stem cells. In the present commentary, we bring to the attention of readers the recent report by Infante et al in the journal of clinical and translational medicine. The TERCELOI cl...

Introduction Infant iron status assessments may be difficult to interpret due to infections. The soluble transferrin receptor (sTfR) has been suggested as a biomarker mainly unaffected by the acute phase response. Reference intervals reflecting dynamics of infant growth first year in life are not well established. Methods The sTfR and CRP concentr...

Purpose of review: Osteogenesis imperfecta (OI) is a chronic disease with few treatment options available. The purpose of this review is to provide an overview on treating OI with mesenchymal stem cells (MSC). Recent findings: Off-the-shelf MSC have a good safety profile and exhibit multilineage differentiation potential and a low immunogenic pr...

Imagine the profits in quality of life that can be made by treating inherited diseases early in life, maybe even before birth! Immense cost savings can also be made by treating diseases promptly. Hence, prenatal stem cell therapy holds great promise for developing new and early-stage treatment strategies for several diseases. Successful prenatal st...

In the original article, Fig. 1A was by mistakenly duplicated. The corrected image is provided in this correction article.

The success of regenerative medicine relies in part on the quality of the cells implanted. Cell cultures from cells isolated from bladder washes have been successfully established but molecular changes and cell characteristics have not been explored in detail. In this work, we analysed the role of telomere shortening in relation to the regenerative...

The present chapter summarizes our current knowledge on fetal stem cell and gene therapy. It focuses on these therapeutic alternatives in regard to past experiences and ongoing and planned studies in humans. Several methodological challenges are discussed that may have wide implications on how these methods could be introduced in clinical practices...

The Boost Brittle Bones Before Birth (BOOSTB4) clinical trial is investigating the safety and efficacy of transplanting fetal derived mesenchymal stromal cells (MSCs) prenatally and/or in early postnatal life to treat severe Osteogenesis Imperfecta (OI). This study aimed to explore stakeholder views to understand perceived benefits or concerns, ide...

Background: Osteogenesis Imperfecta (OI) is a rare genetic condition whose key characteristic is increased bone fragility. OI has the potential to impact upon all family members, making it important to consider the challenges families face, how they cope and their support needs as the affected individual moves from childhood through to adult life....

Maternal microchimerism may arise in the offspring during pregnancy, and may be favorable or unfavorable. Additionally, maternal cells present in umbilical cord blood used for stem cell transplantation may affect the outcome after transplantation. The aim of this study was to evaluate the cellular subset and frequency of maternal cells in umbilical...

Purpose of Review The aim of the study is to provide an overview on the possibility of treating congenital disorders prenatally with mesenchymal stromal cells (MSCs). Recent Findings MSCs have multilineage potential and a low immunogenic profile and are immunomodulatory and more easy to expand in culture. Their ability to migrate, engraft and diff...

Endometriosis is an inflammatory disease marked by ectopic growth of endometrial cells. Mesenchymal stromal cells (MSC) have immunosuppressive properties that have been suggested as a treatment for inflammatory diseases. Therefore, the aim herein was to examine effects of allogeneic MSC on endometriosis-derived cells in vitro as a potential therapy...

Background: Major congenital malformations affect up to 3% of newborns. Infants with prenatally diagnosed soft tissue defects should benefit from having autologous tissue readily available for surgical implantation in the perinatal period. In this study, we investigate fetal subcutaneous cells (fSC) as cellular source for tissue engineering. Meth...

Disrupted organogenesis leads to permanent malformations that may require surgical correction. Autologous tissue grafts may be needed in severe lack of orthotopic tissue but include donor site morbidity. The placenta is commonly discarded after birth and has a therapeutic potential. The aim of this study was to determine if the amnion from placenta...

Background and objective Umbilical cord blood (UCB) is a valuable stem cell source used for transplantation. Immediate umbilical cord (UC) clamping is widely practised, but delayed UC clamping is increasingly advocated to reduce possible infant anaemia. The aim of this study was to investigate an intermediate UC clamping time point and to evaluate...

Endometriosis is an inflammatory disease with predominance of immunosuppressive M2 macrophages in the pelvic cavity that could be involved in the pathology through support and immune escape of ectopic lesions. Mesenchymal stromal cells (MSC) are found in ectopic lesions, and MSC from nonendometriosis sources are known to induce M2 macrophages. Ther...

Staff from the Mayo Clinic in the US and the Karolinska Institute in Sweden describe a joint transatlantic course intended to broaden the horizons of the next generation of researchers in the field of regenerative medicine.

In the era of regenerative medicine, experimental therapies using stem cells are increasing. As with all new interventions, the practices for transfer of relevant information to the trial participants and attaining informed consent are critical parts of the process. When the investigational medicinal product consists of stem cells where all risks h...

Supplementary figure 1. Protein expression of amnion-residing cells. Amnion cultured in DMEM-EC was analyzed for protein expression at day 0 to 21. All cells expressed CD73 and the epithelial cells expressed PCK at all time points. There was a low expression of Ki67 and caspase 3 up to day 14, and at day 21 no Ki67 expression was detected but a sli...

Zielsetzung: Eine effektive Behandlung der Osteogensis imperfecta (OI) existiert bislang nicht. Schwere Formen der OI manifestieren sich bereits intrauterin, die Betroffenen leiden lebenslang unter multiplen Frakturen, Schmerzen, Kleinwuchs sowie orthopadischen Komplikationen. Bisherige Ergebnisse aus 3 Fallen zeigten eine Besserung der Symptome na...

Finding suitable cell sources is one of the main challenges in regenerative medicine. In addition to improving the dysfunctional tissue requiring reconstruction, low immunogenicity is beneficial. Mesenchymal stem cells (MSCs) are immune-privileged multipotent stromal cells that can easily multiply and differentiate along many lineages with a minima...

Osteogenesis Imperfecta (OI) is characterized by severe bone deformities, growth retardation and bones that break easily, often from little or no apparent cause. OI is a genetic disorder primarily with defective type I collagen with a wide spectrum of clinical expression. In the more severe cases it can be diagnosed before birth. Transplantation of...

Congenital malformations are the leading cause of deaths during the neonatal period. Infants with prenatally diagnosed soft tissue defects may benefit from readily available autologous tissue for surgical implantation perinatally. In this study we investigated the cell content of amniotic fluid (AF) and its suitability for isolation and expansion o...

Macroporous bacterial nanocellulose (BNC) scaffolds with calcium phosphate coated surfaces is a candidate for future bone tissue engineering applications. The mineralization of the macroporous BNC scaffolds was achieved by a biomimetic process, resulting in an environment resembling native bone tissues' mineralized extra cellular matrix both topogr...

Osteogenesis imperfecta (OI) can be a severe disorder that can be diagnosed before birth. Transplantation of mesenchymal stem cells (MSC) has the potential to improve the bone structure, growth, and fracture healing. In this review, we give an introduction to OI and MSC, and the basis for pre- and postnatal transplantation in OI. We also summarize...

Mesenchymal stem cells (MSCs) have vast potential in cell therapy, and are experimentally used in the clinic. Therefore, it is critical to find a serum- and xeno-free cryopreservation method. The aim of this study was to compare two serum- and xeno-free cryoprotectants for MSCs. Adipose tissue MSCs (Ad-MSCs) and bone marrow MSCs (BM-MSCs) were cryo...

Background There is a growing interest in mesenchymal stem cells (MSCs) because they are regarded as good candidates for cell therapy. Adipose tissue represents an easily accessible source to derive mesenchymal stem cells (Ad-MSCs) non-invasively in large numbers. The aim of this study was to evaluate a defined serum-free medium for in vitro expans...

Urological reconstructive surgery is sometimes hampered by a lack of tissue. In some cases, autologous urothelial cells (UCs) are not available for cell expansion and ordinary tissue engineering. In these cases, we wanted to explore whether autologous mesenchymal stem cells (MSCs) from bone marrow could be used to create urological transplants. MSC...

Osteogenesis imperfecta (OI) can be recognized prenatally with ultrasound. Transplantation of mesenchymal stem cells (MSCs) has the potential to ameliorate skeletal damage. We report the clinical course of two patients with OI who received prenatal human fetal MSC (hfMSC) transplantation and postnatal boosting with same-donor MSCs. We have previous...

Naturally acquired microchimerism may arise in the mother and her child during pregnancy when bidirectional trafficking of cells occurs through the placental barrier. The occurrence of maternal microchimerism (maternal cells in the offspring) has been associated with several autoimmune diseases, especially in children. Systemic Lupus erythematosus...

Background: Treatment with multipotent mesenchymal stromal cells (MSC) has the potential to ameliorate mesodermal disorders. Objective: To treat severe osteogenesis imperfecta (OI) with fetal MSC. Methods: Ten years ago, we treated a fetus with OI type III (COL1A2: c.3008G>A, p.Gly1003Asp) in utero with fetal HLA-mismatched MSC. The procedure was u...

To develop cell therapies for damaged nervous tissue with human neural stem/progenitor cells (hNPCs), the risk of an immune response and graft rejection must be considered. There are conflicting results and lack of knowledge concerning the immunocompetence of hNPCs of different origin. Here, we studied the immunogenicity and immunomodulatory potent...

Oral mucosal lamina propria progenitor cells (OMLP-PCs) are a novel, clonally derived PC population of neural crest origin with the potential to differentiate down both mesenchymal and neuronal cell lineages. In this study we aimed to determine the immunological properties of OMLP-PCs and to establish whether they would be suitable candidates for a...

Multipotent mesenchymal stromal cells, also known as mesenchymal stem cells (MSC), can be isolated from adult and fetal tissues. Recently, there has been considerable interest in MSC because they have features favorable for transplantation, namely their multipotency and non-immunogenic properties. We analyzed how human MSC derived from first-trimes...

Transplacental passage of circulating first-trimester fetal mesenchymal stem cells (fMSC) raises the prospect of harvesting fetal cells in maternal blood. Despite high sensitivity in model systems, negative selection and culture strategies yield fMSC only rarely in post-termination maternal blood. The different adhesion molecule profile of fMSC to...

Over the past decades fetal medicine with fetal therapy has evolved as a new field within obstetrics. Different treatment strategies have been explored and one of those is fetal stem cell transplantation. The rational for in-utero stem cell transplantation is based on the assumptions that treatment before birth is preferable because the target dise...

The aim of the present study was to analyze the presence of maternal cells in human fetal tissues in the second trimester. Tissues from 11 second-trimester fetuses terminated because of social reasons or because of malformations and/or trisomy were investigated. By cell sorting and polymerase chain reaction amplification, we studied the presence of...

It has been shown recently that human umbilical cord perivascular cells (HUCPVC) are bio-equivalent to bone marrow-derived mesenchymal stromal cells (BM-MSC) in their mesenchymal differentiation and marker expression. HUCPVC populations provide high yields of rapidly proliferating mesenchymal progenitor cells. The question we wished to address, in...

Mesenchymal stromal cells (MSC) may be used in cellular therapy to treat graft-versus-host-disease and autoimmune disorders, and in regenerative medicine. Preliminary data suggest limited cellular allogeneic rejection, but less is known about humoral responses. The objective of this study was to investigate whether antibodies against MSC were prese...

Multipotent mesenchymal stromal cells (MSC) are currently under intense investigation to determine their role in cellular therapy. They are a rare subset of cells, but are easy to isolate and possess an extensive proliferative potential. MSC differentiate into cell types of mesenchymal and nonmesenchymal lineages, providing a promising tool for tis...

Duchenne muscular dystrophy (DMD) is a common X-linked disease resulting from the absence of dystrophin in muscle. Affected boys suffer from incurable progressive muscle weakness, leading to premature death. Stem cell transplantation may be curative, but is hampered by the need for systemic delivery and immune rejection. To address these barriers t...

The biological properties of stem cells are key to the success of cell therapy, for which MSC are promising candidates. Although most therapeutic applications to date have used adult bone marrow MSC, increasing evidence suggests that MSC from neonatal and mid-gestational fetal tissues are more plastic and grow faster. Fetal stem cells have been iso...

To study the subset of maternal cells in fetal tissue in a 2nd-trimester fetus with malformations. By cell sorting and PCR amplification, we studied the presence of maternal CD3+ (T cells), CD19+ (B cells), CD34+ (hematopoietic progenitor cells), and CD45+ (leukocytes) in different tissues in a 2nd trimester fetus. Maternal cells could be detected...

Mesenchymal stem cells (MSC) are progenitor cells that are capable of differentiating into mesenchymal tissues. Fetal and adult MSC have similar morphology but differ in proliferative, differentiating and immunosuppressive properties. Further exploring their differences could help in choosing the right source for cellular therapy. The gene expressi...

Recent evidence suggests that cells with the properties of human mesenchymal stem cells (hMSCs) can be derived from adult peripheral tissues, including adipose tissue, muscle and dermis. We isolated hMSCs from the stromal-vascular portion of subcutaneous adipose tissue from seven adult subjects. These cells could be readily differentiated into cell...

Mesenchymal stem cells (MSC) are progenitors of mesenchymal tissues such as bone, cartilage, and adipose. Adult human leukocyte antigen (HLA)-matched MSC have been used in cellular therapies of bone disorders such as osteogenesis imperfecta, with promising results. A female fetus with multiple intrauterine fractures, diagnosed as severe osteogenesi...

Several families of genes by and large located on the X chromosome encode proteins of unspecified function. Commonly known as cancer/testis (CT) antigens, they are considered, under normal conditions, only to be expressed in cells of the germ line and placenta. CT genes are also often expressed in cancer cells, hence their classification. Here we r...

Mesenchymal stem cells (MSC) are immunomodulatory and inhibit lymphocyte proliferation. We studied surface expression of lymphocyte activation markers and secreted cytokines, when lymphocytes were activated in the presence of MSC. MSC suppressed the proliferation of phytohaemagglutinin (PHA)-stimulated CD3+, CD4+ and CD8+ lymphocytes. MSC significa...

Adult bone-marrow-derived mesenchymal stem cells are immunosuppressive and prolong the rejection of mismatched skin grafts in animals. We transplanted haploidentical mesenchymal stem cells in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver. Clinical response was striking. The patient is now we...

Mesenchymal stem cells (MSCs) can be isolated from adult bone marrow and fetal liver. We investigated the immunologic properties of undifferentiated and differentiated human fetal MSCs. Expression of HLA class I and II was investigated by flow cytometry and Western blot on undifferentiated fetal MSC and after in vitro differentiation to adipocytes...

The function of adipocytes derived from human mesenchymal stem cells (hMSC) was investigated for the first time in hMSC from fetal liver (FL) and adult bone marrow (BM) and compared with preadipocytes from human subcutaneous adipose tissue differentiated according to adipocyte-specific protocols. FL- and BM-derived adipocytes displayed both morphol...

Adult mesenchymal stem cells (MSCs) have been suggested to decrease lymphocyte proliferation in vitro. We hypothesised that foetal MSCs (fMSCs) would have an immunosuppressive effect on allograft responses in vitro. Human MSCs were isolated and cultured from first-trimester foetal livers and characterised by flow cytometry. fMSC stained positive fo...