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Clinical Trial
. 2023 Jun 15;12(6):355-364.
doi: 10.1093/stcltm/szad027.

A Pilot Phase I Trial of Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells in Neonates With Hypoxic-Ischemic Encephalopathy

Charles Michael Cotten  1 , Kimberley Fisher  1 , William Malcolm  1 , Kathryn E Gustafson  2 , Lynn Cheatham  3 , Amanda Marion  1 , Rachel Greenberg  1 , Joanne Kurtzberg  3
Affiliations
Clinical Trial

A Pilot Phase I Trial of Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells in Neonates With Hypoxic-Ischemic Encephalopathy

Charles Michael Cotten et al. Stem Cells Transl Med. .

Abstract

Hypoxic ischemic encephalopathy (HIE) in neonates causes increased mortality and long-term morbidity in surviving babies. Hypothermia (HT) has improved outcomes, however, mortality remains high with ~half of surviving babies developing neurological impairment in their first years. We previously explored the use of autologous cord blood (CB) to determine if CB cells could lessen long-term damage to the brain. However, the feasibility of CB collection from sick neonates limited the utility of this approach. Allogeneic cord tissue mesenchymal stromal cells (hCT-MSC), cryopreserved and readily available, have been shown to ameliorate brain injury in animal models of HIE. We, therefore, conducted a pilot, phase I, clinical trial to test the safety and describe the preliminary efficacy of hCT-MSC in neonates with HIE. The study treated infants with moderate to severe HIE, treated with HT, with 1 or 2 doses of 2 million cells/kg/dose of hCT-MSC given intravenously. The babies were randomized to receive 1 or 2 doses with the first dose during HT and the second dose 2 months later. Babies were followed for survival and development with scoring of Bayley's at 12 postnatal months. Six neonates with moderate (4) or severe (2) HIE were enrolled. All received 1 dose of hCT-MSC during HT and 2 received a 2nd dose, 2 months later. hCT-MSC infusions were well tolerated although 5/6 babies developed low titer anti-HLA antibodies by 1 year of age. All babies survived, with average to low-average developmental assessment standard scores for ages between 12 and 17 postnatal months. Further study is warranted.

Keywords: HIE; cord tissue; hypothermia; mesenchymal stromal cells; neonates.

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Conflict of interest statement

Duke Licensed data and regulatory packages regarding manufacturing, characterization, and clinical use of hCT-MSCs to CryoCell International (Oldsmar, FL). Drs. Cotten and Kurtzberg receive payments as inventors of this technology through this licensing agreement. Two patents, 2021-0361716 and WO2019195554, have been submitted and are under review. C.M.C. declared intellectual property rights in CryoCell International and have received royalties as income. Duke licensed data and regulatory packages related to this work with CryoCell International and advisory roles with ReAlta Life Sciences and Origins Bioscience. R.G.G. declared advisory role with Propharm, Inc. Tellus Therapeutics. J.K. declared Intellectual property rights with Duke and CryoCell; licensing agreement with SinoCell and Duke and advisory roles with Consultant for Neurogene and Mesoblast.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
CONSORT diagram of screened and enrolled infants.
See this image and copyright information in PMC

References

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