1. Sixth Annual Meeting of International Society for Stem Cell Research (ISSCR), Philadelphia, PA USA, 11th - 14th June 2008.
“Autologous Bone Marrow stem cells for treatment of Oral Sub-Mucous Fibrosis - a case report”.

2. 8th Annual Meeting of Japanese Society of Regenerative Medicine, Tokyo, Japan, 5th - 6th March 2009.
"Autologous Bone Marrow Stem Cells in Oral Submucous Fibrosis – Our experience in three cases with six months follow-up".

Autologous Bone Marrow stem cells for treatment of Oral Sub-Mucous Fibrosis - a case report
Sankaranarayanan S (1), Padmanaban J (2), Ramachandran CR (3), Manjunath S (4), Baskar S (4), Senthil Kumar R (4), Senthil Nagarajan R (4), Murugan P (4), Srinivasan V (4), Abraham S (5).

1. Raja Muthiah Dental College, Chidambaram, India.
2. Melmaruvathur Medical College, Melmaruvathur, India.
3. Raja Muthiah Dental College, Chennai, India.
4. Nichi-In centre for Regenerative Medicine, Chennai, India
5. Yamanashi University School of Medicine, Kofu Shi, Japan.

Background: Oral Sub-Mucous Fibrosis (OSMF) is a chronic disease of insidious onset featuring the deposition of fibrosis tissues in the sub-mucosal layer of the pharynx, palate, fauces, cheek, lips, pharynx and esophagus. Due to this, lumen size of the vessels decrease and also a decrease in number of capillaries occur culminating in a decrease in blood supply to the epithelium in the affected region. The underlying muscles of mastication are also affected (Mokal et al. 2005) and it restricts the mouth opening. Despite the application of several treatment modalities, none of them have produced satisfactory results. Here we report our experience with one such case where autologous bone marrow mononuclear cells were injected with an aim of increasing angiogenesis to reverse the pathological changes mentione above.

Materials and Methods: A 43 yrs olf male patient suffering from OSMF for the past 10 yrs who was treated 3 yrs before with cortisone injection and by other adjunctive medical management with no improvement was treated by this method. He had the complications such as severe burning sensation, difficulty in swallowing, severe blanching, restricted mouth opening of 30mm and xerostomia. Pre-injection biopsy was taken to confirm the pathology and also carcinoma was ruled out, 40 ml of Bone Marrow was aspirated from posterior iliac crest, transported in Acid Citrate Dextrose and was processed for mononuclear cells (MNC) by Ficoll density gradient centrifugation, following the cGMP protocols. The 4 mL of MNC concentreate containing 294 millions was ijected intra orally at various sites in the affected area under local anesthesia.

Results: The patient did not show any improvement till4 weeks after the stem cell injection. From then, he as gradually started showing relief from burning sensation, increased salivary secretion and a 4mm increase in the mouth opening. H&E stain comparison of pre and post injection biopsy showed signs of angiogenesis with increase in number of capillaries, return of wavy pattern of collagen fibres with less inflammatory cell infiltration indicating the degrenulation of the fibrous tissue and loosely organised connective tissue, all indicating a resumption towards a normal histology.

Conclusion: This case report of an autologus bone marros stek cell injection in Oral Sub-Mucosal Fibrosis before it turns to be a carcinoma has been safe and efficient. We need a larger study with long term followu-up in similar cases before applying this modality for treatment in routine clinical practice.

Autologous Bone Marrow Stem Cells in Oral Submucous Fibrosis – Our experience in three cases with six months follow-up
Abraham S (1,5,6), Sankaranarayanan S (2), Padmanaban J (3), Manimaran K (4), Srinivasan V(5), Senthil Nagarajan R (5), Murugan P (5), Manjunath S (5), Senthil Kumar R (5,6), Baskar S (5,6).

1. Yamanashi University School of Medicine, Kofu Shi, Japan.
2. Karpagavinayagar Dental College, India.
3. Melmaruvathur Dental College, India.
4. Ramakrishna Dental College, India.
5. Nichi-In centre for Regenerative Medicine, India
6. Nichi-Asia centre, Malaysia.

Background: Oral Submucous Fibrosis (OSF) is a chronic disease of insidious onset featuring the deposition of fibrosis tissues in the submucosal layer of the oral cavity. Current treatments are not effective. Here we report our experience with 3 such cases treated with Autologous Bone Marrow Stem Cells (ABMSC).

Materials and Methods: Three male patients of age 28,43 and 74 with a history of 9, 10 and 6 years of OSF respectively were given injection of ABMSC, after current treatment had failed. 40-50ml of Bone marrow was aspirated. 175~294 millions of mononuclear cells were injected in the affected site under local anesthesia. patients were followed up for symptoms and histology.

Results: Complete relief from burning sensation and increased salivary secretion resulted in all. Mouth opening increased by 3-7 mm. Histology revealed change of the amorphous collagen into wavy form & reduction in inflammatory infiltrate, a resumption towards normalcy.

Conclusion: This study shows ABMSCs to be efficient and safe with no adverse reaction in OSF. The consistency of the results is an added advance and more cases to be studies.