Autologous transplantation of umbilical cord blood-derived cells in extreme preterm infants: protocol for a safety and feasibility study

IntroductionPreterm brain injury continues to be an important complication of preterm birth, especially in extremely premature infants. Umbilical cord blood-derived cells (UCBCs) are increasingly being evaluated for their neuroprotective and neuroreparative properties in preclinical and clinical studies. There remains a paucity of information on the feasibility and safety of autologous UCBC transplantation in extremely premature infants.Methods and analysisA single centre safety and feasibility study in preterm babies born before 28 weeks gestation. Cord blood will be collected after birth and if sufficient blood is obtained, UCB mononuclear cells will be harvested from the cord blood, characterised and stored. After excluding infants who have already suffered severe preterm brain injury, based on cranial ultrasounds in first week of life, preterm infants will be infused with autologous UCBCs via the intravenous route at a dose of 25–50 million UCBCs/kg body weight of live cells, with the cell number being the maximum available up to 50 million cells/kg. A minimum of 20 infants will be administered autologous UCBCs. Primary outcomes will include feasibility and safety. Feasibility will be determined by access to sufficient cord blood at collection and UCBCs following processing. Safety will be determined by lack of adverse events directly related to autologous UCBC administration in the first few days after cell administration. Secondary outcomes studied will include neonatal and neurodevelopmental morbidities till 2 years of life. Additional outcomes will include cell characteristics of all collected cord blood, and cytokine responses to cell administration in transplanted infants till 36 weeks’ corrected age.Ethics and disseminationMonash Health Human Research Ethics Committee approved this study in December 2019. Recruitment is to commence in July 2020 and is expected to take around 12 months. The findings of this study will be disseminated via peer-reviewed journals and at conferences.Trial registration numberACTRN12619001637134.

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Soft Tissue Repair with Easy-Accessible Autologous Newborn Placenta or Umbilical Cord Blood in Severe Malformations: A Primary Evaluation

Stem Cells International ◽

10.1155/2017/1626741 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10

Author(s):

Åsa Ekblad ◽

Magdalena Fossum ◽

Cecilia Götherström

Keyword(s):

Soft Tissue ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Mononuclear Cells ◽

Therapeutic Potential ◽

Donor Site ◽

Autologous Transplantation ◽

Donor Site Morbidity ◽

Primary Evaluation

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 or plasma rich of growth factors (PRGF) with mononuclear cells (MNC) from umbilical cord blood (UCB), collected noninvasively, could be used as bio-constructs for autologous transplantation as an easy-accessible no cell culture-required method. Human amnion and PRGF gel were isolated and kept in culture for up to 21 days with or without small intestine submucosa (SIS). The cells in the constructs showed a robust phenotype without induced increased proliferation (Ki67) or apoptosis (caspase 3), but the constructs showed decreased integrity of the amnion-epithelial layer at the end of culture. Amnion-residing cells in the SIS constructs expressed CD73 or pan-cytokeratin, and cells in the PRGF-SIS constructs expressed CD45 and CD34. This study shows that amnion and UCB are potential sources for production of autologous grafts in the correction of congenital soft tissue defects. The constructs can be made promptly after birth with minimal handling or cell expansion needed.

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Use of Acellular Umbilical Cord-Derived Tissues in Corneal and Ocular Surface Diseases

Medicines ◽

10.3390/medicines8020012 ◽

2021 ◽

Vol 8 (2) ◽

pp. 12

Author(s):

Arianna A. Tovar ◽

Ian A. White ◽

Alfonso L. Sabater

Keyword(s):

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Ocular Surface ◽

Cellular Proliferation ◽

Mononuclear Cells ◽

Autologous Serum ◽

High Concentration ◽

Ocular Surface Diseases ◽

Natural Healing

Blood derived products have become a valuable source of tissue for the treatment of ocular surface diseases that are refractory to conventional treatments. These can be obtained from autologous or allogeneic sources (patient’s own blood or from healthy adult donors/umbilical cord blood, respectively). Allogeneic cord blood demonstrates practical advantages over alternatives and these advantages will be discussed herein. Umbilical cord blood (UCB) can be divided, generally speaking, into two distinct products: first, mononuclear cells, which can be used in regenerative ophthalmology, and second, the plasma/serum (an acellular fraction), which may be used in the form of eyedrops administered directly to the damaged ocular surface. The rationale for using umbilical cord serum (UCS) to treat ocular surface diseases such as severe dry eye syndrome (DES), persistent epithelial defects (PED), recurrent epithelial erosions, ocular chemical burns, graft versus host disease (GVHD), among others, is the considerably high concentration of growth factors and cytokines, mimicking the natural healing properties of human tears. Allogeneic serum also offers the opportunity for therapeutic treatment to patients who, due to poor heath, cannot provide autologous serum. The mechanism of action involves the stimulation of endogenous cellular proliferation, differentiation and maturation, which is highly efficient in promoting and enhancing corneal epithelial healing where other therapies have previously failed.

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Umbilical cord blood therapy modulates neonatal hypoxic ischemic brain injury in both females and males

Scientific Reports ◽

10.1038/s41598-021-95035-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tayla R. Penny ◽

Yen Pham ◽

Amy E. Sutherland ◽

Joohyung Lee ◽

Graham Jenkin ◽

...

Keyword(s):

Brain Injury ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Significant Risk ◽

Immunohistochemical Analysis ◽

Significant Risk Factor ◽

Tissue Loss ◽

Artery Ligation ◽

Rat Pups

AbstractPreclinical and clinical studies have shown that sex is a significant risk factor for perinatal morbidity and mortality, with males being more susceptible to neonatal hypoxic ischemic (HI) brain injury. No study has investigated sexual dimorphism in the efficacy of umbilical cord blood (UCB) cell therapy. HI injury was induced in postnatal day 10 (PND10) rat pups using the Rice-Vannucci method of carotid artery ligation. Pups received 3 doses of UCB cells (PND11, 13, 20) and underwent behavioural testing. On PND50, brains were collected for immunohistochemical analysis. Behavioural and neuropathological outcomes were assessed for sex differences. HI brain injury resulted in a significant decrease in brain weight and increase in tissue loss in females and males. Females and males also exhibited significant cell death, region-specific neuron loss and long-term behavioural deficits. Females had significantly smaller brains overall compared to males and males had significantly reduced neuron numbers in the cortex compared to females. UCB administration improved multiple aspects of neuropathology and functional outcomes in males and females. Females and males both exhibited injury following HI. This is the first preclinical evidence that UCB is an appropriate treatment for neonatal brain injury in both female and male neonates.

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Umbilical cord blood CD34+ cells administration improved neurobehavioral status and alleviated brain injury in a mouse model of cerebral palsy

Child s Nervous System ◽

10.1007/s00381-021-05068-0 ◽

2021 ◽

Author(s):

Yanqun Chang ◽

Shouheng Lin ◽

Yongsheng Li ◽

Song Liu ◽

Tianbao Ma ◽

...

Keyword(s):

Stem Cells ◽

Cerebral Palsy ◽

Brain Injury ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Neonatal Rat ◽

Hematopoietic Stem ◽

Long Term Study ◽

Hsc Transplantation

Abstract Purpose Cerebral palsy (CP) is the most common neuromuscular disease in children, and currently, there is no cure. Several studies have reported the benefits of umbilical cord blood (UCB) cell treatment for CP. However, these studies either examined the effects of UCB cell fraction with a short experimental period or used neonatal rat models for a long-term study which displayed an insufficient immunological reaction and clearance of human stem cells. Here, we developed a CP model by hypoxia-ischemic injury (HI) using immunodeficient mice and examined the effects of human UCB CD34+ hematopoietic stem cells (HSCs) on CP therapy over a period of 8 weeks. Methods Sixty postnatal day-9 (P9) mouse pups were randomly divided into 4 groups (n = 15/group) as follows: (1) sham operation (control group), (2) HI-induced CP model, (3) CP model with CD34+ HSC transplantation, and (4) CP model with CD34- cell transplantation. Eight weeks after insult, the sensorimotor performance was analyzed by rotarod treadmill, gait dynamic, and open field assays. The pathological changes in brain tissue of mice were determined by HE staining, Nissl staining, and MBP immunohistochemistry of the hippocampus in the mice. Results HI brain injury in mice pups resulted in significant behavioral deficits and loss of neurons. Both CD34+ HSCs and CD34- cells improved the neurobehavioral statuses and alleviated the pathological brain injury. In comparison with CD34- cells, the CD34+ HSC compartments were more effective. Conclusion These findings indicate that CD34+ HSC transplantation was neuroprotective in neonatal mice and could be an effective therapy for CP.

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