Novel Use of Intraarticular Granulocyte Colony Stimulating Factor (hG-CSF) Combined with Activated Autologous Peripheral Blood Stem Cells Mobilized with Systemic hG-CSF: Safe and Efficient in Early Osteoarthritis

Cartilage ◽  
2021 ◽  
pp. 194760352110495
Author(s):  
Konstantinos I. Papadopoulos ◽  
Mantana Paisan ◽  
Warachaya Sutheesophon ◽  
Thana Turajane

Osteoarthritis (OA) tends to occur in older individuals frequently burdened with comorbidities and diverse pharmacological interactions. As articular cartilage has low regenerative power, potent local tissue engineering approaches are needed to support chondrogenic differentiation. Acellular preparation methods as well as approaches to coax endogenous reparative cells into the joint space appear to have limited success. Supported by our in-vitro and clinical studies, we propose that our novel intra-articular administration of human granulocyte colony stimulating factor (IA-hG-CSF) combined with autologous activated peripheral blood stem cells (AAPBSC) is safe and offers treatment advantages not seen with other cellular interventions in early osteoarthritis.

Blood ◽  
1995 ◽  
Vol 85 (6) ◽  
pp. 1655-1658 ◽  
Author(s):  
WI Bensinger ◽  
CH Weaver ◽  
FR Appelbaum ◽  
S Rowley ◽  
T Demirer ◽  
...  

Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increased risk of graft- versus-host-disease (GVHD) from the large number of T cells infused. Eight patients with advanced malignancies received allogeneic PBSC transplants from genotypically HLA-identical sibling donors. All donors received 5 days of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 16 micrograms/kg/day) subcutaneously and were leukapheresed for 2 days. After treatment of the patient with total body irradiation and cyclophosphamide (n = 7) or etoposide, thiotepa, and cyclophosphamide (n = 1), PBSCs were infused immediately after collection and without modification. All patients received cyclosporine and either methotrexate (n = 6) or prednisone (n = 2) for GVHD prophylaxis, rhG-CSF was well tolerated with mild bone pain requiring acetaminophen occurring in two donors. All patients engrafted and in seven hematopoietic recovery was rapid, with 500 neutrophils/microL achieved by day 18 and 20,000 platelets/microL by day 12. Complete donor engraftment was documented by Y chromosome analysis in all four sex-mismatched donor-recipient pairs tested and by DNA analysis in two sex-matched pairs. One patient died on day 18 of veno-occlusive disease of the liver with engraftment but before chromosome analysis could be performed (results are pending in 1 patient). A second patient died of fungal infection 78 days after transplant. Grade 2 acute GVHD occurred in two patients and grade 3 GVHD occurred in one patient. One patient is 301 days from transplant in remission with chronic GVHD; the remaining five patients are alive and disease free 67 to 112 days after transplantation. Preliminary results indicate that allogeneic PBSCs mobilized by rhG-CSF can provide rapid hematologic recovery without an appreciably greater incidence of acute GVHD than would be expected with marrow. Further follow-up is required to determine the incidence of chronic GVHD and any potential beneficial effects on relapse after transplant.


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