Bone Marrow Mononuclear Cells Transplantation in Treatment of Established Bronchopulmonary Dysplasia: A Case Report

Background

Bronchopulmonary dysplasia (BPD), first described by Northway in 1967, is becoming more common in newborns with low birth weight and those who receive prolonged mechanical ventilation [1,2]. Despite great advances in perinatal care, the prognosis of BPD is still poor [3,4]. To date, there are few effective treatments to improve outcomes of BPD. Recently, stem cell (STC) transplantation has been tested in the management of BPD in animals. In hyperoxia-induced mice, STC transplantation reduced alveolar loss and lung inflammation, and prevented pulmonary hypertension. STC transplantation has been reported to attenuate alveolar and vascular injury, and decrease fibrosis [5–10].

Before 2014, there was no evidence available for using STC transplantation to treat established BPD in humans. In 2014, Chang published a report of 9 infants at high risk of developing BPD who received stem cells to prevent BPD [11,12].

This case study reports a preterm infant with established BPD who was successfully treated by autologous bone marrow mononuclear cell transplantation.

Case Report

INVESTIGATIONS ON ADMISSION:

Arterial blood gases with the FiO₂ of 24%; pH 7.39, PaCO₂: 43.7 mmHg, PaO₂: 56 mmHg), BE: ±2, HCO₃: 26.2, lactate: 1.99 mmol/l. Total blood cell count was WBC: 12 G/l; neutrophils: 12.3%; lymphocytes: 73.8% platelets: 344 G/l; and Hb: 10.1 g/dl.

On hospital day 4, a chest CT demonstrated diffuse fibrosis in both lungs, atelectasis in the upper lobes of both lungs, and significant air trapping in both lower lobes (Figure 3). BM MNC transplantation was indicated because, after long-term treatment, he could not be weaned from the oxygen supply after intensive treatment with corticosteroids.

After approval from the Hospital Scientific Committee and written informed consent from patient’s parents, the infant underwent BM MNCs transplantation on hospital day 22, at 4000 gr weight. The patient was anesthetized and 32 ml of bone marrow was extracted from the iliac crests. Our previous experience showed that 8 ml of bone marrow per kg body weight can be harvested safely in children [13].

BM MNCs were extracted from 32 ml bone marrow by density gradient centrifugation using Ficoll-Paque (GE Healthcare, Sweden). The final product contained 620×10⁶ of MNCs, which were supplemented by autologous plasma up to a total of 9 ml.

The BM MNCs were characterized by flow cytometry with monoclonal antibodies specific for CD45, and CD34, conjugated with R Phycoerythrin (PE) and fluorescein isothiocyanate (FITC), respectively (Beckman Coulter, CA, USA). Cells were analyzed by Navios Cytometer (Beckman Coulter, USA). The final product contained 43.85 × 10^{^}6 of hHSC, which had CD45 dim CD34+ phenotype. Data were collected and recorded using Navios software, version 3.2.

A volume of 0.5 ml of the extracted liquid diluted with 0.5 ml NaCl 0.9% was instilled 4 times via the endotracheal tube every 30 min.

Results

Discussion

This is the first trial using autologous BM MNCs to treat an infant with established BPD. Clinical and chest CT improvements were observed and demonstrated in our patient.

Over time, different sources of MNCs have been used to treat BPD in animals [5–10]. In humans, in 2014 and 2017, Chang et al. used cord blood mononuclear cell transplantation for preterm infants at risk of BPD, without severe adverse effects [11,12]. In this case, we demonstrated the use of autologous BM MNCs to treat established BPD. The extraction of bone marrow from the infant iliac was practical and suggests this is an alternative stem cell source when cord blood is not available.

The route of STC transplantation is still under consideration. Chang reported that intratracheal injection is safe in preterm infants [11]. However, in this case, intratracheal injection of STC resulted in bronchial obstruction and new-onset pulmonary arterial hypertension. These complications should be recognized early and managed expediently. As a result, the remaining MNCs were delivered intravenously. We conclude that the combined intratracheal and intravenous approach is a good alternative, depending on patient response.

Conclusions

The results of this study suggest that BM MNCs reduces lungs fibrosis and improves respiratory function of BPD. This approach offers promising treatment of BPD.