Umbilical Cord Stem Cells for Graft-versus-Host Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Kansas Medical Center
Must not be taking: Investigational agents
Disqualifiers: Medical, psychiatric conditions, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This study evaluates the safety and effectiveness of two different doses of umbilical cord derived, ex-vivo cultured and expanded Wharton's jelly mesenchymal stem cells (MSCTC-0010) in the treatment of acute Graft versus Host Disease (aGVHD). The first 5 participants enrolled in the study will receive a lower dose of MSCTC-0010. If none of the first 5 participants have treatment-related serious adverse events (TRSAEs) for 42 days, then the next 5 participants will receive a slightly higher dose of MSCTC-0010.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, you cannot have received any other investigational agent for acute GVHD treatment in the 30 days before joining the trial.
What data supports the effectiveness of the treatment MSCTC-0010, Umbilical Cord-Derived Wharton's Jelly Mesenchymal Stem Cells, for Graft-versus-Host Disease?
Research shows that mesenchymal stem cells from Wharton's jelly of the umbilical cord can improve the environment for blood stem cells, help them grow, and reduce immune responses, which may help in treating Graft-versus-Host Disease.
12345Is it safe to use umbilical cord stem cells for treating Graft-versus-Host Disease?
Research shows that umbilical cord-derived mesenchymal stem cells, including those from Wharton's jelly, have been studied for their safety in various conditions. They are considered to have low risk of immune rejection and have been used in clinical trials for conditions like Graft-versus-Host Disease, indicating a general safety profile in humans.
678910How is the treatment MSCTC-0010 different from other treatments for graft-versus-host disease?
MSCTC-0010 is unique because it uses mesenchymal stem cells derived from the Wharton's jelly of the umbilical cord, which are easily obtained and processed, have low risk of immune rejection, and do not raise ethical concerns compared to other stem cell sources.
111121314Eligibility Criteria
Adults aged 18-75 with acute Graft versus Host Disease after an allogenic transplant at Kansas University Cancer Center. They must use two forms of contraception if of childbearing potential and cannot have used other investigational agents for aGVHD within the last 30 days. Those with medical or psychiatric conditions that could affect trial participation are excluded.Inclusion Criteria
I am between 18 and 75 years old.
Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use two forms of adequate contraception (hormonal AND barrier method of birth control) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately.
You are using hormonal birth control like the pill, implant, injection, or have an intrauterine device (IUD) for birth control.
+8 more
Exclusion Criteria
Participants may not have received any other investigational agent used to treat acute GVHD for 30 days prior to enrollment.
Participant has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the participant.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a lower dose of MSCTC-0010 and are observed for treatment-related serious adverse events and response
42 days
1 visit (in-person)
Dose Escalation
Participants receive an increased dose of MSCTC-0010 and are observed for treatment-related serious adverse events and response
42 days
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including the occurrence of additional immunosuppressive therapy and ectopic tissue formation
90 days
Participant Groups
The trial is testing two doses of Wharton's jelly mesenchymal stem cells (MSCTC-0010) for treating aGVHD. The first group receives a lower dose, and if safe, the next group gets a higher dose. Safety is monitored by looking out for serious adverse events over 42 days.
1Treatment groups
Experimental Treatment
Group I: MSCTC-0010 Dose EscalationExperimental Treatment1 Intervention
Cohort 1: First 5 participants will receive a lower dose of cord-blood derived Wharton's jelly mesenchymal stem cells (MSCTC-0010) and they will be observed for 42 days after the dose for treatment-related serious adverse events (TRSAE) and response.
Cohort 2: Second 5 participants will receive an increased dose of MSCTC-0010 and will be observed for 42 days after the dose for TRSAE and response.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Kansas University Cancer CenterKansas City, KS
Loading ...
Who Is Running the Clinical Trial?
University of Kansas Medical CenterLead Sponsor
References
Mesenchymal stem cells from the Wharton's jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture. [2021]Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow-derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton's jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated.
Cord blood CD34+ cells expanded on Wharton's jelly multipotent mesenchymal stromal cells improve the hematopoietic engraftment in NOD/SCID mice. [2018]This study aims to investigate the capability of Wharton's jelly multipotent mesenchymal stromal cells (WJ-MSC) to support the in vitro expansion of hematopoietic stem/progenitor cells (HSPC) derived from cord blood (CB) in the absence of exogenous cytokines, and the effect on engraftment of the expanded cells in a mouse model.
[Research Advance on Role of Umbilical Cord Mesenchymal Stem Cell in Hematopoietic Stem Cells Transplantation-Review]. [2018]Hematopoietic stem cell transplantation is an important method for the treatment of hematological malignancies. The hematopoietic recovery after transplantation, graft-versus-host disease (GVHD) prevention and treatment are the key to affect transplant success. Umbilical cord mesenchymal stem cells (hUC-MSC) can improve the hematopoietic microenvironment, promote hematopoietic stem cell homing and hematopoietic recovery, support hematopoiesis. In aduition, the hUC-MSC have immune function for a variety of immune cells, can avoid and alleviate the host immune response, have a certain effect on the treatment of GVHD. This article reviews the research advances on umbilical cord mesenchymal stem cells in hematopoietic stem cell transplantation.
Mesenchymal stem cells derived from Wharton's Jelly of the umbilical cord: biological properties and emerging clinical applications. [2022]In recent years there seems to be an unbounded interest concerning mesenchymal stem cells (MSCs). This is mainly attributed to their exciting characteristics including long-term ex vivo proliferation, multilineage potential and immunomodulatory properties. In this regard MSCs emerge as attractive candidates for various therapeutic applications. MSCs were originally isolated from the bone marrow (BM) and this population is still considered as the gold standard for MSC applications. Nevertheless the BM has several limitations as source of MSCs, including MSC low frequency in this compartment, the painful isolation procedure and the decline in MSC characteristics with donor's age. Thus, there is accumulating interest in identifying alternative sources for MSCs. To this end MSCs obtained from the Wharton's Jelly (WJ) of umbilical cords (UC) have gained much attention over the last years since they can be easily isolated, without any ethical concerns, from a tissue which is discarded after birth. Furthermore WJ-derived MSCs represent a more primitive population than their adult counterparts, opening new perspectives for cell-based therapies. In this review we will at first give an overview of the biology of WJ-derived UC-MSCs. Then their potential application for the treatment of cancer and immune mediated disorders, such graft versus host disease (GVHD) and systemic lupus erythematosus (SLE) will be discussed, and finally their putative role as feeder layer for ex vivo hematopoietic stem cell (HSC) expansion will be pointed out.
Human umbilical cord Wharton's jelly stem cells and its conditioned medium support hematopoietic stem cell expansion ex vivo. [2022]Bone marrow mesenchymal stromal cells (BMMSCs) have been used as feeder support for the ex vivo expansion of hematopoietic stem cells (HSCs) but have the limitations of painful harvest, morbidity, and risk of infection to the patient. This prompted us to explore the use of human umbilical cord Wharton's jelly MSCs (hWJSCs) and its conditioned medium (hWJSC-CM) for ex vivo expansion of HSCs in allogeneic and autologous settings because hWJSCs can be harvested in abundance painlessly, are proliferative, hypoimmunogenic, and secrete a variety of unique proteins. In the presence of hWJSCs and hWJSC-CM, HSCs put out pseudopodia-like outgrowths and became highly motile. Time lapse imaging showed that the outgrowths helped them to migrate towards and attach to the upper surfaces of hWJSCs and undergo proliferation. After 9 days of culture in the presence of hWJSCs and hWJSC-CM, MTT, and Trypan blue assays showed significant increases in HSC numbers, and FACS analysis generated significantly greater numbers of CD34(+) cells compared to controls. hWJSC-CM produced the highest number of colonies (CFU assay) and all six classifications of colony morphology typical of hematopoiesis were observed. Proteomic analysis of hWJSC-CM showed significantly greater levels of interleukins (IL-1a, IL-6, IL-7, and IL-8), SCF, HGF, and ICAM-1 compared to controls suggesting that they may be involved in the HSC multiplication. We propose that cord blood banks freeze autologous hWJSCs and umbilical cord blood (UCB) from the same umbilical cord at the same time for the patient for future ex vivo HSC expansion and cell-based therapies.
Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy. [2020]The paper presents current evidence on the properties of human umbilical cord-derived mesenchymal stem cells, including origin, proliferative potential, plasticity, stability of karyotype and phenotype, transcriptome, secretome, and immunomodulatory activity. A review of preclinical studies and clinical trials using this cell type is performed. Prospects for the use of mesenchymal stem cells, derived from the umbilical cord, in cell transplantation are associated with the need for specialized biobanking and transplant standardization criteria.
Differentiation of umbilical cord mesenchymal stem cells into steroidogenic cells in comparison to bone marrow mesenchymal stem cells. [2021]Human umbilical cord can be obtained easily and it represents a non-controversial source of mesenchymal stem cells (MSCs) and umbilical cord Wharton's jelly-derived MSCs (UC-MSCs) have low immunogenicity. In this study, UC-MSCs were induced to become steroidogenic cells and compared to bone marrow-derived MSCs (BM-MSCs).
Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. [2022]To assess the safety and feasibility of allogeneic human umbilical cord blood (hUCB)-derived mesenchymal stem cell (MSC) transplantation in preterm infants.
Wharton's jelly-derived stromal cells and their cell therapy applications in allogeneic haematopoietic stem cell transplantation. [2022]For decades, mesenchymal stromal cells (MSCs) have been of great interest in the fields of regenerative medicine, tissue engineering and immunomodulation. Their tremendous potential makes it desirable to cryopreserve and bank MSCs to increase their accessibility and availability. Postnatally derived MSCs seem to be of particular interest because they are harvested after delivery without ethical controversy, they have the capacity to expand at a higher rate than adult-derived MSCs, in which expansion decreases with ageing, and they have demonstrated immunological and haematological supportive properties similar to those of adult-derived MSCs. In this review, we focus on MSCs obtained from Wharton's jelly (the mucous connective tissue of the umbilical cord between the amniotic epithelium and the umbilical vessels). Wharton's jelly MSCs (WJ-MSCs) are a good candidate for cellular therapy in haematology, with accumulating data supporting their potential to sustain haematopoietic stem cell engraftment and to modulate alloreactivity such as Graft Versus Host Disease (GVHD). We first present an overview of their in-vitro properties and the results of preclinical murine models confirming the suitability of WJ-MSCs for cellular therapy in haematology. Next, we focus on clinical trials and discuss tolerance, efficacy and infusion protocols reported in haematology for GVHD and engraftment.
Isolation and characterisation of mesenchymal stem cells from different regions of the human umbilical cord. [2022]Umbilical cords as a source of stem cells are of increasing interest for cell therapies as they present little ethical consideration and are reported to contain immune privileged cells which may be suitable for allogeneic based therapies. Mesenchymal stem cells (MSCs) sourced from several different cord regions, including artery, vein, cord lining, and Wharton's jelly, are described in the literature. However, no one study has yet isolated and characterised MSCs from all regions of the same cord to determine the most suitable cells for cell based therapeutics.
MSCs can be differentially isolated from maternal, middle and fetal segments of the human umbilical cord. [2018]Human Wharton's jelly-derived mesenchymal stromal cells (hWJMSCs) are possibly the most suitable allogeneic cell source for stromal cell therapy and tissue engineering applications because of their hypo-immunogenic and non-tumorigenic properties, easy availability and minimal ethical concerns. Furthermore, hWJMSCs possess unique properties of both adult mesenchymal stromal cells and embryonic stromal cells. The human umbilical cord (UC) is approximately 50-60 cm long and the existing studies in the literature have not provided information on which segment of the UC was studied. In this study, hWJMSCs derived from three anatomical segments of the UC are compared.
Human mesenchymal stem cells derived from umbilical cord and bone marrow exert immunomodulatory effects in different mechanisms. [2020]Mesenchymal stem cells (MSCs) are an attractive tool to treat graft-versus-host disease because of their unique immunoregulatory properties. Although human bone marrow-derived MSCs (BM-MSCs) were the most widely used MSCs in cell therapy until recently, MSCs derived from human umbilical cords (UC-MSCs) have gained popularity as cell therapy material for their ethical and noninvasive collection.
Method to isolate mesenchymal-like cells from Wharton's Jelly of umbilical cord. [2018]The umbilical cord is a noncontroversial source of mesenchymal-like stem cells. Mesenchymal-like cells are found in several tissue compartments of the umbilical cord, placenta, and decidua. Here, we confine ourselves to discussing mesenchymal-like cells derived from Wharton's Jelly, called umbilical cord matrix stem cells (UCMSCs). Work from several laboratories shows that these cells have therapeutic potential, possibly as a substitute cell for bone marrow-derived mesenchymal stem cells for cellular therapy. There have been no head-to-head comparisons between mesenchymal cells derived from different sources for therapy; therefore, their relative utility is not understood. In this chapter, the isolation protocols of the Wharton's Jelly-derived mesenchymal cells are provided as are protocols for their in vitro culturing and storage. The cell culture methods provided will enable basic scientific research on the UCMSCs. Our vision is that both umbilical cord blood and UCMSCs will be commercially collected and stored in the future for preclinical work, public and private banking services, etc. While umbilical cord blood banking standard operating procedures exist, the scenario mentioned above requires clinical-grade UCMSCs. The hurdles that have been identified for the generation of clinical-grade umbilical cord-derived mesenchymal cells are discussed.
Transplantation of human umbilical mesenchymal stem cells from Wharton's jelly after complete transection of the rat spinal cord. [2022]Human umbilical mesenchymal stem cells (HUMSCs) isolated from Wharton's jelly of the umbilical cord can be easily obtained and processed compared with embryonic or bone marrow stem cells. These cells may be a valuable source in the repair of spinal cord injury.