Umbilical Cord Stem Cells for Graft-versus-Host Disease

Overseen By Kerry Hepler

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Kansas Medical Center

Must not be taking: Investigational agents

Disqualifiers: Medical, psychiatric conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 42 days

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using umbilical cord stem cells to determine their safety and effectiveness in treating acute Graft-versus-Host Disease (aGVHD), a condition where transplanted cells attack the body. Participants will receive one of two doses of these special cells, starting with a lower dose and, if safe, progressing to a slightly higher dose. The trial seeks individuals who have undergone an allogenic transplant at the University of Kansas Medical Center and are experiencing moderate to severe aGVHD unresponsive to steroids. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that MSCTC-0010, a treatment using stem cells from umbilical cords, is generally safe for people. Earlier studies tested two different doses of MSCTC-0010 in patients with acute Graft versus Host Disease (aGVHD) and found that patients handled the treatment well. No serious side effects or unexpected tissue growth were linked to the treatment. These findings suggest the treatment might be safe, but since this is early research, ongoing monitoring is necessary to confirm these results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for graft-versus-host disease, which often include immunosuppressive drugs, MSCTC-0010 uses stem cells derived from Wharton's jelly in umbilical cords. This innovative approach is exciting because these mesenchymal stem cells have the potential to modulate the immune response more naturally, possibly reducing the risk of severe immune reactions. Researchers are particularly interested in MSCTC-0010 for its potential to offer a more targeted and less toxic way to manage the disease, improving patient outcomes.

What evidence suggests that MSCTC-0010 might be an effective treatment for acute Graft versus Host Disease?

Research shows that stem cells from umbilical cord tissue, known as Wharton's jelly mesenchymal stem cells (MSCTC-0010), may help treat acute Graft versus Host Disease (aGVHD). Earlier studies found this treatment safe, with no serious side effects. In this trial, participants will receive either a low or high dose of MSCTC-0010. Patients who received both doses in previous studies responded well, indicating that these cells can help reduce aGVHD symptoms. The stem cells lower inflammation and aid healing, which could benefit people with aGVHD. Overall, early findings suggest that MSCTC-0010 might effectively manage this condition. ^{1 2 4 5 6}

Who Is on the Research Team?

Joseph McGuirk, MD

Principal Investigator

The University of Kansas - Cancer Center

Are You a Good Fit for This Trial?

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

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.

A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• MSCTC-0010

Trial Overview 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.

How Is the Trial Designed?

Group I: MSCTC-0010 Dose Escalation Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Published Research Related to This Trial

Transplantation of human umbilical mesenchymal stem cells (HUMSCs) into rats with complete spinal cord transection led to significant improvements in locomotion and increased regeneration of axons, indicating their potential for spinal cord repair.

HUMSCs not only survived for 16 weeks post-transplantation but also produced various growth factors that may aid in healing, while reducing inflammation in the spinal cord, suggesting a dual role in promoting recovery and minimizing damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of human umbilical mesenchymal stem cells from Wharton's jelly after complete transection of the rat spinal cord. Yang, CC., Shih, YH., Ko, MH., et al.[2022]

Wharton's jelly multipotent mesenchymal stromal cells (WJ-MSC) can effectively support the in vitro expansion of hematopoietic stem/progenitor cells (HSPC) from cord blood without the need for added cytokines, achieving significant increases in cell numbers (2.0 and 7.3 times after 7 and 13 days, respectively).

The expanded HSPC showed improved engraftment in a mouse model, with 100% of mice receiving day-7 co-cultured cells successfully engrafted compared to 75% for the control, indicating that WJ-MSC not only preserve the CD34+ population but also enhance the repopulating ability of these cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood CD34+ cells expanded on Wharton's jelly multipotent mesenchymal stromal cells improve the hematopoietic engraftment in NOD/SCID mice. Milazzo, L., Vulcano, F., Barca, A., et al.[2018]

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) from Wharton's jelly have been shown to effectively support the growth of hematopoietic stem cells (HSCs) from cord blood in long-term culture assays, similar to bone marrow-derived MSCs (BM-MSCs).

The study suggests that UC-MSCs could be used therapeutically to provide a supportive environment for cord blood HSCs, potentially allowing for cotransplantation of HSCs and UC-MSCs, which could enhance the success of stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Bakhshi, T., Zabriskie, RC., Bodie, S., et al.[2021]

Umbilical cord matrix stem cells (UCMSCs) derived from Wharton's Jelly show promising therapeutic potential as an alternative to bone marrow-derived mesenchymal stem cells, although direct comparisons between different sources of mesenchymal cells have not been conducted.

The chapter outlines protocols for isolating, culturing, and storing UCMSCs, aiming to facilitate research and future clinical applications, while also addressing the challenges in generating clinical-grade UCMSCs for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Method to isolate mesenchymal-like cells from Wharton's Jelly of umbilical cord. Seshareddy, K., Troyer, D., Weiss, ML.[2018]

Umbilical cord mesenchymal stem cells (hUC-MSC) can enhance the recovery of hematopoietic stem cells after transplantation, which is crucial for the success of treating blood cancers.

hUC-MSCs also have immune-modulating properties that can help prevent and treat graft-versus-host disease (GVHD), a common complication after hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Research Advance on Role of Umbilical Cord Mesenchymal Stem Cell in Hematopoietic Stem Cells Transplantation-Review]. Qiao, SM., Wang, Y., Song, XL., et al.[2018]

Mesenchymal stem cells (MSCs) from Wharton's Jelly of umbilical cords are a promising alternative to traditional bone marrow-derived MSCs due to their easier isolation, ethical advantages, and more primitive characteristics, which may enhance their therapeutic potential.

WJ-derived MSCs show potential applications in treating cancer and immune-mediated disorders, such as graft versus host disease and systemic lupus erythematosus, and may also serve as a supportive layer for expanding hematopoietic stem cells in laboratory settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cells derived from Wharton's Jelly of the umbilical cord: biological properties and emerging clinical applications. Batsali, AK., Kastrinaki, MC., Papadaki, HA., et al.[2022]

Human Wharton's jelly-derived mesenchymal stromal cells (hWJMSCs) from the maternal and fetal segments of the umbilical cord show higher viability and proliferation rates compared to those from the middle segment, making them more suitable for therapeutic applications.

All three segments of hWJMSCs can differentiate into bone, fat, and cartilage cells, but the maternal and fetal segments demonstrate significantly better differentiation potential, indicating their preference for use in tissue engineering and regenerative medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MSCs can be differentially isolated from maternal, middle and fetal segments of the human umbilical cord. Lim, J., Razi, ZR., Law, J., et al.[2018]

Both umbilical cord-derived mesenchymal stem cells (UC-MSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) show similar abilities to suppress graft-versus-host disease, making them effective options for cell therapy.

UC-MSCs have distinct immunoregulatory mechanisms, such as higher expression of prostaglandin E2 and IL-6, and they are more effective at inhibiting T helper 17 cells and inducing regulatory T cells compared to BM-MSCs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human mesenchymal stem cells derived from umbilical cord and bone marrow exert immunomodulatory effects in different mechanisms. Song, Y., Lim, JY., Lim, T., et al.[2020]

The study demonstrated that intratracheal transplantation of allogeneic human umbilical cord blood-derived mesenchymal stem cells (MSCs) in 9 preterm infants was safe and well tolerated, with no serious adverse effects observed.

Transplant recipients showed a reduction in inflammatory markers and lower severity of bronchopulmonary dysplasia (BPD) compared to historical controls, suggesting potential therapeutic benefits that warrant further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. Chang, YS., Ahn, SY., Yoo, HS., et al.[2022]

Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) exhibit promising properties such as high proliferative potential, stability in genetic makeup, and significant immunomodulatory activity, making them suitable for therapeutic applications.

The review highlights the importance of biobanking and standardization in the use of UC-MSCs for cell transplantation, emphasizing the need for rigorous protocols to ensure safety and efficacy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy. Arutyunyan, I., Elchaninov, A., Makarov, A., et al.[2020]

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have a higher potential for steroidogenic differentiation compared to bone marrow-derived MSCs (BM-MSCs), making them a promising option for therapies targeting steroid hormone deficiencies.

UC-MSCs not only showed greater expression of steroidogenic genes and higher hormone secretion (like testosterone and cortisol) but also demonstrated better cell viability and proliferative potential than BM-MSCs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiation of umbilical cord mesenchymal stem cells into steroidogenic cells in comparison to bone marrow mesenchymal stem cells. Wei, X., Peng, G., Zheng, S., et al.[2021]

Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs) show great promise for cellular therapy in haematology, particularly in supporting haematopoietic stem cell engraftment and modulating immune responses like Graft Versus Host Disease (GVHD).

These postnatally derived MSCs can be cryopreserved for future use, have a higher expansion rate compared to adult-derived MSCs, and present no ethical concerns, making them a valuable resource in regenerative medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wharton's jelly-derived stromal cells and their cell therapy applications in allogeneic haematopoietic stem cell transplantation. Pochon, C., Notarantonio, AB., Laroye, C., et al.[2022]

Umbilical cords are a promising source of mesenchymal stem cells (MSCs) for cell therapies due to their ethical advantages and potential immune privilege, making them suitable for treatments that do not require a perfect match.

This study highlights the need for research that isolates and characterizes MSCs from all regions of the same umbilical cord to identify the best candidates for therapeutic use, as current literature lacks comprehensive comparisons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and characterisation of mesenchymal stem cells from different regions of the human umbilical cord. Mennan, C., Wright, K., Bhattacharjee, A., et al.[2022]

Human umbilical cord Wharton's jelly mesenchymal stromal cells (hWJSCs) and their conditioned medium (hWJSC-CM) can effectively support the ex vivo expansion of hematopoietic stem cells (HSCs) without the painful and risky harvesting associated with bone marrow, showing significant increases in HSC numbers after 9 days of culture.

The hWJSC-CM contains higher levels of key proteins and interleukins that promote HSC proliferation, suggesting a promising alternative for future therapies by potentially freezing hWJSCs and umbilical cord blood together for patient-specific treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human umbilical cord Wharton's jelly stem cells and its conditioned medium support hematopoietic stem cell expansion ex vivo. Fong, CY., Gauthaman, K., Cheyyatraivendran, S., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03158896

Evaluation of Umbilical Cord-Derived Wharton's Jelly Stem ... This study evaluates the safety and effectiveness of two different doses of umbilical cord derived, ex-vivo cultured and expanded Wharton's jelly mesenchymal ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9289888/

A Phase I Study to Evaluate Two Doses of Wharton's Jelly ... A two-dose cohort trial allogeneic Wharton's Jelly-derived mesenchymal stromal cells (WJMSC, referred to as MSCTC-0010, here) were tested in 10 patients with ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32740891/

A Phase I Study to Evaluate Two Doses of Wharton's Jelly ... Treatment of patients with de novo HR or SR aGVHD with low or high dose MSCTC-0010 was safe: the infusion was well-tolerated, and no TRAEs or ectopic tissue ...

4. trialx.com trialx.com/clinical-trials/listings/249624/evaluation-of-umbilical-cord-derived-whartons-jelly-stem-cells-for-the-treatment-of-acute-graft-versus-host-disease/?&geo_lat=38.9822282&geo_lng=-94.6707917&radius=10&place=Overland%20Park&user_country=United%20States

Evaluation of Umbilical Cord-Derived Wharton's Jelly Stem ... This study evaluates the safety and effectiveness of two different doses of umbilical cord derived, ex-vivo cultured and expanded Wharton's ...

5. patlynk.com patlynk.com/trial/NCT03158896

Evaluation of Umbilical Cord-Derived Wharton's Jelly Stem ... This study evaluates the safety and effectiveness of two different doses of umbilical cord derived, ex-vivo cultured and expanded Wharton's jelly ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725004646

391 A Phase Ib Study to Expand on the Safety of Wharton's ... MSCYC-0010, an umbilical cord-derived mesenchymal stromal cell product with potent immunosuppressive effects, was studied in a First-in-Human Phase 1 ...