Long-term outcome of human cord blood-derived hematopoietic progenitor cells in murine lungs

Abstract

Intranasally delivered human cord blood-derived CD34+ hematopoietic progenitor cells have the capacity to engraft and undergo transdifferentiation to surfactant-containing alveolar epithelial type II cell-like cells in lungs of newborn mice. The aim of this study was to determine the long-term fate of such transplanted cells as well as their effects on alveolar development in neonatally injured lungs. Double transgenic CCSP+/FasL+ mice with inducible lung-specific FasL expression, targeted to induce respiratory epithelial apoptosis in the perinatal period, served as model of neonatal lung injury. Non-injured single transgenic CCSP+/FasL- littermates served as controls. Freshly isolated umbilical cord blood CD34+ cells (0.5 to 1.0×10(6)) were administered at postnatal day 5 by intranasal inoculation; sham controls received equal volume PBS. Engraftment, alveolar epithelial differentiation, lung growth, and alveolarization were evaluated one year after transplantation. Engrafted cord blood-derived cells, detected by human-specific FISH (fluorescent in situ hybridization) analysis, and cord blood-derived alveolar type II-like cells, detected by double immunofluorescence analysis, while sparse, were seen in all conditions and more frequent in double than single transgenic recipients. The total lung volume and volume of air-exchanging parenchyma, assessed by stereological volumetry, were significantly greater in CD34-treated double transgenic animals than in PBS-treated double transgenic controls. Alveolarization, assessed by histomorphometry, was equivalent in these groups. These results suggest that transdifferentiated alveolar epithelial cells, derived from cord blood CD34+ cells, can persist up to one year after intrapulmonary delivery. Cord blood-CD34+ cell administration appears to have growth-promoting effects in injured newborn lungs, without affecting alveolar development in this model.

Are all stem cells equal? Systematic review, evidence map, and meta-analyses of preclinical stem cell-based therapies for bronchopulmonary dysplasia

“…Different from this were “probably beneficial” therapies which included ECFC, hAEC, CB CD 34+, Mononuclear CD 34+, and BM Ckit+ . Furthermore, two studies with Mononuclear cells (MNC) (different animal species, route, hyperoxia duration and the dose of MNCs), one study with MSCs (intranasal route) and one with embryonic EPC, concluded that these therapies were not effective. Conversely, four therapies, EPC Cultured (aberrant tissue formation in lungs and inflammation), miPSC (cystic teratomas), mESC (fibrosarcomas), and hiPSC (lung teratomas and perivascular infiltration of the lungs, liver, heart, and kidneys) were found to be harmful, although the translational potential of these therapies remains circumspect, as the rationale behind the use of these cells in the primary studies remains unclear.…”

“…Yet there has been no systematic review to assess the extent of current evidence regarding safety and efficacy of cell-based therapies in preclinical BPD and identify gaps that could jeopardize successful clinical translation. studies), [26][27][28][29]32,34,35,37,39,40,42,43,48,49,[51][52][53][55][56][57][58][59][61][62][63]66,[68][69][70]72,73,[75][76][77][78] human amniotic epithelial cells (hAEC, n = 4), 36,64,65,74 mononuclear CD34 + (n = 4), 27,30,46,47 endothelial colony forming cells (ECFC, n = 3), 46,64,70 endothelial progenitor cells (EPCs, n = 3), 31,41,71 bone marrow derived angiogenic cells (BMDAC, n = 1), 71 bone marrow derived (BM) ckit+ cells (n = 1), 50 cord blood CD34 + (n = 1), 44 human amniotic fluid stem cells (hAFSC, n = 1), 33 human-induced pluripotent...…”

“…53 In contrast, fewer "Cell-free" therapies were investigated, and these included MSC-derived conditioned media (CdM, n = 6), 34,35,48,49,56,66 ECFC-Conditioned media (CdM, n = 2), 38,60 or MSC-derived exosomes (n = 1). 67 The control groups were most often treated with saline (n = 32) [26][27][28][29][30][31][32]34,37,40,44,46,47,49,51,52,[56][57][58][59]61,62,64,65,[68][69][70][71][72][74][75][76][77] or with a control cell/ cell-free media (n = 12). 33,35,46,[48][49][50]53,…”

Upregulation of Vascular Endothelial Growth Factor in Amniotic Fluid Stem Cells Enhances Their Potential to Attenuate Lung Injury in a Preterm Rabbit Model of Bronchopulmonary Dysplasia

“…Therapeutic delivery of MSC to the lungs has been done under various conditions (delivery route, dose, and timing) in mice, rats, and lamb BPD models [18-22]. When comparing delivery routes of MSC in hyperoxia-exposed rats, marginally better results were obtained with intratracheal compared to intraperitoneal and intravenous delivery [23].…”

Ovarian adult stem cells: hope or pitfall?

“…However, if the presence of Mvh in the bone marrow is a strong witness for their plea, there are reports of transdifferentiated HSC, either from bone marrow donors or own circulating HSC, into adult stem cells of other injured organs (e.g. lung, [22] liver [23], heart [24]). Without previous aggression (chemotherapy, irradiation) however, BM transplant does not seems to contribute to GSC ovarian pool [25].…”