Characterization of a novel decellularized bone marrow scaffold as an inductive environment for hematopoietic stem cells

2019 ◽  
Vol 7 (4) ◽  
pp. 1516-1528 ◽  
Author(s):  
Juares E. Romero Bianco ◽  
Renata Giardini Rosa ◽  
Ada Congrains-Castillo ◽  
Paulo P. Joazeiro ◽  
Stephen D. Waldman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Bovine Bone ◽  
Hematopoietic Stem ◽  
Bone Marrow Study ◽  
Increasing Demand

Due to the increasing demand for a bone marrow study model, we developed a natural scaffold from decellularized bovine bone marrow (DeBM).

Preliminary phenotypic characterization of hematopoietic and non-hematopoietic stem cells from stimulated bone marrow without expansion for its use in cellular therapy

Cytotherapy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. S81
Author(s):  
C. Mancias-Guerra ◽  
I. Velasco-Ruiz ◽  
S. Sanchez-Garcia ◽  
R. Huerta-Rangel ◽  
N. Mendez-Ramirez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Cellular Therapy ◽  
Phenotypic Characterization ◽  
Hematopoietic Stem

Hematopoietc Stem Cell Targeted Neonatal Gene Therapy Cures oc/oc Mice from Osteopetrosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 456-456
Author(s):  
Johan Richter ◽  
Maria Johansson ◽  
Teun J. de Vries ◽  
Mats Ehinger ◽  
Vince Everts ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Bovine Bone ◽  
Wild Type ◽  
Hematopoietic Stem

Abstract Infantile malignant osteopeterosis (IMO) is a progressive, rare autosomal recessive disorder affecting osteoclast function. 50% of the affected children have a mutation in the Tcirg1 gene coding for one subunit of an osteoclast specific proton pump, OC116. The non-resorbed dense, sclerotic bones cause symptoms including pancytopenia and progressive visual loss and ultimately death. So far, the only curative treatment is hematopoietic stem cell (HSC) transplantation. The oc/oc mouse has a mutation in the gene homologous to Tcirg1 giving rise to similar symptoms as in patients leading to death of the mice at the age of 3–4 weeks. We have previously shown that the oc/oc mouse can be successfully treated with neonatal transplantation of normal HSC leading to prolonged survival and reversal of osteopetrosis (M. Johansson et al., Exp. Hematology34;242, 2006). In the current study we set out to develop HSC directed gene therapy for osteopetrosis in the oc/oc mouse model. As the bone marrow compartment is severely reduced in the oc/oc mouse fetal liver (FL) cells depleted of Ter119+ erythroid cells were used as a source of hematopoietic stem cells. We first established that wild type Ter119 depleted FL cells marked with a GFP vector and transplanted to newborn oc/oc mice i.p. could correct the osteopetrotic phenotype just as was shown for fresh bone marrow cells previously. Subsequently, Ter119 depleted FL cells from oc/oc mice were transduced with a retroviral vector expressing OC116 and GFP. In vitro transduction efficiency was 60–85%. One-day-old oc/oc mice were irradiated (400cGy) and transplanted i.p. with the transduced FL cells (1–3.5x106). 7 out of 14 mice survived past the expected lifespan and had 8–53% GFP+ cells in the peripheral blood at 3, 6 and 12 weeks. Analysis of bone structure with X-ray and histopathology showed an improvement at 8 weeks and an almost normal structure at 18 weeks, indicating induction of osteoclast activity. In vitro culture of osteoclasts from bone marrow from transplanted animals on bovine bone slices showed GFP marked osteoclasts and bone resorption, albeit at lower levels than for wild type cells. In the oc/oc mouse there is a block in B-lymphopoiesis leading to a reduced number of B-lymphocytes in the peripheral blood. In treated mice a reversal of this deficiency was observed. In summary we have demonstrated that the osteoclast defect seen in oc/oc mice can be successfully corrected by neonatal transplantation of gene modified hematopoietic stem cells and that this can lead to long-term survival of treated mice. This represents a significant step towards the development of gene therapy for osteopetrosis.

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